RESUMEN

Glomerulonephritis (GN) is the most common cause of end-stage renal failure worldwide; in most cases, it cannot be cured and can only delay the progression of the disease. At present, the main treatment methods include symptomatic therapy, immunosuppressive therapy, and renal replacement therapy. However, effective treatment of GN is hindered by issues such as steroid resistance, serious side effects, low bioavailability, and lack of precise targeting. With the widespread application of nanoparticles in medical treatment, novel methods have emerged for the treatment of kidney diseases. Targeted transportation of drugs, nucleic acids, and other substances to kidney tissues and even kidney cells through nanodrug delivery systems can reduce the systemic effects and adverse reactions of drugs and improve treatment effectiveness. The high specificity of nanoparticles enables them to bind to ion channels and block or enhance channel gating, thus improving inflammation. This review briefly introduces the characteristics of GN, describes the treatment status of GN, systematically summarizes the research achievements of nanoparticles in the treatment of primary GN, diabetic nephropathy and lupus nephritis, analyzes recent therapeutic developments, and outlines promising research directions, such as gas signaling molecule nanodrug delivery systems and ultrasmall nanoparticles. The current application of nanoparticles in GN is summarized to provide a reference for better treatment of GN in the future.

Asunto(s)

Nefropatías Diabéticas , Glomerulonefritis , Nefritis Lúpica , Humanos , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/metabolismo , Riñón/metabolismo , Nanotecnología

RESUMEN

Purpose: To estimate the cost-effectiveness of Nefecon in addition to the best supportive care (BSC) vs BSC in a hypothetical cohort of commercially insured adult patients with primary immunoglobulin A nephropathy (IgAN) from a United States (US) societal perspective. Methods: A lifetime horizon, semi-Markov model was developed that consisted of nine health states: chronic kidney disease (CKD) stage 1, 2, 3a, 3b, 4, end-stage renal disease (ESRD) with dialysis, ESRD without dialysis, post-kidney transplant, and death. Health state occupancy was estimated from individual patient-level data from the Phase 3 randomized controlled trial NefIgArd Part A (NCT03643965). Additional scenarios evaluated the impact of varying the time horizon, discounting, costs included, rounds of treatment, and the method used to calculate transition probabilities. Results: In the deterministic base case analysis over a lifetime horizon, Nefecon plus BSC (hereafter Nefecon) had an incremental cost of $3,810 vs BSC. Nefecon resulted in a mean survival gain of 0.247 quality-adjusted life years (QALYs), 0.195 life years (LYs), and 0.244 equal value life years (evLYs) vs BSC alone - this resulted in incremental cost-effectiveness ratios (ICERs) of $15,428 per QALY, $19,502 per LY, and $15,611 per evLY gained. Probabilistic sensitivity analyses estimated that with willingness to pay thresholds of $100,000, $150,000, and $250,000 per QALY gained, Nefecon would be cost-effective over BSC in 66.70%, 75.02%, and 86.82% of cases, respectively. In the scenario analysis, Nefecon remained cost-effective with 4 rounds of treatment. Conclusion: Nefecon was associated with LY and QALY gains vs BSC, with an incremental cost of $3,810. Based on these values, with a willingness to pay threshold of $100,000 per QALY gained, Nefecon was found to be a cost-effective treatment for US adults with primary IgAN.

RESUMEN

Primary glomerular disease was the leading cause of chronic kidney disease (CKD) in China; however, changes in the economy and environment introduce variations in the spectrum of kidney diseases. This study aimed to analyze renal biopsy data to inform disease prevention and public health interventions. In this retrospective cohort study, data from 2,803 consecutive renal biopsies conducted at our center between January 2010 and December 2018 were analyzed. The sample was disaggregated by age and the date of biopsy to facilitate analysis. Primary glomerulonephritis (PGN) is the most frequent (81.84%) finding, followed by secondary glomerulonephritis (SGN; 15.38%), tubulointerstitial nephritis (15.38%), and others (1.57%). IgA nephropathy (IgAN), idiopathic membranous nephropathy (iMN), and minimal change disease were the primary causes of PGN. Among PGN cases, the incidence of iMN arose, especially among those aged ≥ 60 years old, during the observation period. Contrary to the case of iMN, the proportion of IgAN in PGN trended downward, continuously, and at length. Moreover, IgAN mainly affected those aged 25-44 years old and less so those aged ≥ 60 years old. Lupus nephritis, Henoch-Schönlein purpura nephritis, and diabetic nephropathy (DN) were key causes of SGN. A ratio reversal between infectious disease and chronic disease dramatically changed SGN patterns. In the past year, the incidence of hepatitis B-related nephritis has constantly declined; however, the proportion of DN among SGN had steadily increased. The incidence of iMN significantly increased during these years. Among SGN cases, the proportion of DN has increased.

Asunto(s)

Nefropatías Diabéticas , Glomerulonefritis por IGA , Glomerulonefritis Membranosa , Glomerulonefritis , Adulto , China/epidemiología , Nefropatías Diabéticas/patología , Glomerulonefritis/epidemiología , Glomerulonefritis/patología , Glomerulonefritis por IGA/epidemiología , Glomerulonefritis por IGA/patología , Glomerulonefritis Membranosa/epidemiología , Glomerulonefritis Membranosa/patología , Humanos , Riñón/patología , Persona de Mediana Edad , Estudios Retrospectivos

RESUMEN

Primary glomerulonephritis is a major global health concern and a disorder with significant heritable components. Rapid advances in sequencing technologies have led to genome-wide, high-throughput investigations of the genetic basis of complex human traits. Genetic studies have successfully mapped several susceptibility loci and disease-causing genes for different subtypes of primary glomerulonephritis. These studies have revealed that IgA nephropathy-associated genes have a highly complex, polygenic and pleiotropic genetic architecture and that genetic susceptibility to membranous nephropathy may be driven by a few large-effect loci. Furthermore, both susceptibility genes and high-penetrant gene mutations reportedly contribute to the development of the most heterogeneous phenotype of focal segmental glomerulosclerosis. The genetic heterogeneity between each glomerular disease type and within different populations has indicated disease-specific and ethnicity-specific underlying molecular mechanisms for the disorders. The findings from genome-wide association studies (GWAS) have mainly included variants on or near the major histocompatibility (MHC) loci, highlighting the molecular basis for the shared pathogenesis of the immune-mediated disease. Recent studies with increased sample sizes and higher resolutions of genome-wide imputation have provided novel insights into the pathogenesis of glomerular disorders. Further integration of results from genomic studies with functional genomics datasets can indicate novel targets for drug discovery as well as potential tools for patient diagnosis and stratification. However, larger GWASs and sequencing studies in independent cohorts and more standardized inclusion of phenotypes across studies are required for each subtype of glomerular disease.

Asunto(s)

Glomerulonefritis por IGA , Glomerulonefritis Membranosa , Glomerulonefritis , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Glomerulonefritis/diagnóstico , Glomerulonefritis/genética , Glomerulonefritis/patología , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/genética , Glomerulonefritis por IGA/patología , Glomerulonefritis Membranosa/patología , Humanos

RESUMEN

BACKGROUND: The prevalence and distribution of glomerular diseases differ among countries, and the indication to perform a kidney biopsy varies among centres. In this study, we assessed the prevalence of primary and secondary glomerulopathies based on histological diagnoses, and the correlation between glomerulopathies and demographic and clinical data was evaluated. METHODS: In this study, 1051 kidney biopsies were retrospectively reviewed between 2000 and 2018. Patient demographic, clinical and laboratory data were assessed. The prevalence of primary glomerulonephritis (PG) and secondary glomerulopathies (SG), as well as tubulointerstitial diseases (TIDs), hereditary nephropathies (HNs) and other diagnoses, were determined. The frequency of primary and secondary glomerulopathies was evaluated by age group, and the temporal variation in frequencies across three time periods (2000-2005, 2006-2011, and 2012-2018) was reported. RESULTS: The prevalence of SG predominated (52.4%), followed by PG (29.6%), other diagnoses (10.7%), TID (6.6%) and HN (1.1%). Among the primary forms of glomerular disease, focal segmental glomerulosclerosis (FSGS) was the most common (37.3%), followed by IgA nephropathy (IgAN, 24.4%), membranous nephropathy (MN, 18.6%) and minimal change disease (MCD, 8.4%). Lupus nephritis (LN, 41.1%) was most common in patients with SG, followed by diabetic kidney disease (DKD, 17.8%), systemic vasculitis (SV, 10.2%) and secondary FSGS (2nd FSGS, 10%). Nephrotic syndrome was the most common clinical presentation in patients with PG and also in patients with DRD and 2nd FSGS, whereas in patients with IgAN and SV, nephritic syndrome was the main presentation. For the age group between 18 and 50 years, LN, FSGS and IgAN predominated; for patients aged between 51 and 65 years, the proportion of DKD and 2nd FSGS increased, and SV was more common in patients > 65 years. The temporal variation in PG across the three time periods showed a statistically significant increase in IgAN (p = 0.001) and a reduction in FSGS over time (p < 0.001). In SG, there was a reduction in LN (p = 0.027) and an increase in DKD (p < 0.001) over time, with a tendency for 2nd FSGS to decrease over time (p = 0.053). CONCLUSIONS: In the studied kidney biopsy registry, FSGS and IgAN were the most prevalent diagnoses in patients with PG, and LN and DKD were the most prevalent in patients with SG. Nephrotic syndrome was the major indication for biopsy. When comparing the temporal variation in glomerulopathies, there was a reduction in FSGS and an increase in IgAN in patients with PGs over time, and for patients with SGs, there was a reduction in LN with an increase in cases of DKD over time.

Asunto(s)

Enfermedades Renales/patología , Glomérulos Renales/patología , Adolescente , Adulto , Biopsia , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Centros de Atención Terciaria , Adulto Joven

RESUMEN

BACKGROUND: Rare diseases (RDs) encompass many difficult-to-treat conditions with different characteristics often associated with end-stage renal disease (ESRD). However, data about transplant outcomes in adult patients are still lacking and limited to case reports/case series without differentiation between immunological/non-immunological RDs. METHODS: Retrospective analysis among all adult kidney transplanted patients (KTs) with RDs (RDsKT group) performed in our high-volume transplantation center between 2005 and 2016. RDs were classified according to the Orphanet code system differentiating between immunological and non-immunological diseases, also comparing clinical outcomes and temporal trends to a control population without RDs (nRDsKT). RESULTS: Among 1381 KTs, 350 patients (25.3%) were affected by RDs (RDsKTs). During a f/up > 5 years [median 7.9 years (4.8-11.1)], kidney function and graft/patient survival did not differ from nRDsKTs. Considering all post-transplant complications, RDsKTs (including, by definition, patients with primary glomerulopathy except on IgA nephropathy) have more recurrent and de-novo glomerulonephritis (14.6% vs. 9.6% in nRDsKTs; p = 0.05), similar rates of de-novo cancers, post-transplant diabetes, dysmetabolism, hematologic disorders, urologic/vascular problems, and lower infectious episodes than nRDsKTs (63.7% vs 72.7%; p = 0.013). Additional stratification for immunological and non-immunological RDsKTs or transplantation periods (before/after 2010) showed no differences or temporal trends between groups. CONCLUSIONS: Kidney transplant centers are deeply involved in RDs management. Despite their high-complex profile, both immunological and non-immunological RDsKTs experienced favorable patients' and graft survival.

Asunto(s)

Enfermedades del Sistema Inmune/epidemiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Enfermedades Raras/epidemiología , Adulto , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Enfermedades del Sistema Inmune/etiología , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Italia/epidemiología , Estimación de Kaplan-Meier , Fallo Renal Crónico/complicaciones , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Prevalencia , Enfermedades Raras/etiología , Estudios Retrospectivos , Factores de Riesgo

RESUMEN

BACKGROUND AND OBJECTIVES: Bacterial infection-related GN occurs concurrent to or after known or unknown infections. It is important to understand the clinical implications of the bacterial isolates, antimicrobial resistance patterns, and effect of latency-based classification on kidney and patient outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In total, 501 consecutive adults diagnosed with bacterial infection-related GN between 2005 and 2017 were included from a biopsy registry of 15,545 patients at a single center in South India, and follow-up data were collected from electronic medical records until December 2019. Latency was defined as time between resolution of infection and onset of GN, which was classified as parainfectious, peri-infectious, or postinfectious GN. Longitudinal kidney and patient outcomes were studied. RESULTS: The mean age of the cohort was 40 (± 15) years, 6% were above 65 years, and 330 (66%) were men. Diabetes was present in 93 (19%) patients. Seventy percent (353 of 501) of patients had known infections, with the median latent period for parainfectious (115 of 353, 33%), peri-infectious (97 of 353, 27%), and postinfectious (141 of 353, 40%) GN being 0, 5 (4-7), and 15 (10-31) days, respectively. The most common predisposing organism was Streptococcus pyogenes (137 of 353, 39%). Drug-resistant nonstreptococcal bacteria were methicillin-resistant Staphylococcus aureus (25%, four of 16), extended-spectrum ß-lactamases (20%, 12 of 59), and carbapenem-resistant organisms (10%, six of 59). Twenty of 22 (91%) of the drug-resistant organisms were isolated from the parainfectious group. The most common site of infection was skin in peri- (23 of 97, 24%) and postinfectious GN (61 of 141, 43%), and urinary tract in parainfectious GN (35 of 115, 30%). Of 321 patients with >3 months of follow-up, 48 (15%) developed kidney failure over a median period of 10 (2-37) months and 14 (4%) died. Parainfectious GN, eGFR<30 ml/min per 1.73 m2, moderate-to-severe interstitial fibrosis and tubular atrophy, and nontreatment with renin-angiotensin system blockers were significant risk factors for progression to kidney failure by a Cox proportional-hazards model. CONCLUSIONS: Along with clinical and histologic predictors, parainfectious GN caused predominantly by nonstreptococcal and drug-resistant bacterial infections was associated with poor kidney prognosis.

Asunto(s)

Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/microbiología , Glomerulonefritis/microbiología , Glomerulonefritis/fisiopatología , Insuficiencia Renal/fisiopatología , Adulto , Atrofia , Biopsia , Carbapenémicos , Farmacorresistencia Bacteriana , Femenino , Fibrosis , Tasa de Filtración Glomerular , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/patología , Humanos , Riñón/patología , Masculino , Staphylococcus aureus Resistente a Meticilina , Persona de Mediana Edad , Sistema de Registros , Insuficiencia Renal/etiología , Estudios Retrospectivos , Factores de Riesgo , Enfermedades Cutáneas Bacterianas/complicaciones , Enfermedades Cutáneas Bacterianas/microbiología , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/microbiología , Infecciones Estreptocócicas/complicaciones , Infecciones Estreptocócicas/microbiología , Streptococcus pyogenes , Factores de Tiempo , Infecciones Urinarias/complicaciones , Adulto Joven , beta-Lactamasas

RESUMEN

Despite improvements in understanding the pathogenic mechanisms of primary glomerular diseases, therapy still remains nonspecific. We sought to identify novel therapies targeting kidney-intrinsic injury of distinct primary glomerulonephritides through computational systems biology approaches. We defined the unique transcriptional landscape within kidneys from patients with focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN) and thin basement membrane nephropathy (TBMN). Differentially expressed genes were functionally annotated with enrichment analysis, and distinct biological processes and pathways implicated in each primary glomerular disease were uncovered. Finally, we identified novel drugs and small-molecule compounds that may reverse each glomerulonephritis phenotype, suggesting they should be further tested as precise therapy in primary glomerular diseases.

RESUMEN

PURPOSE: To identify the clinical characteristics, histopathological features, and prognosis of kidney disease in a large cohort of elderly patients from Northeast China. METHODS: We retrospectively analyzed the renal disease spectrum in 7,122 patients who underwent renal biopsies at the Second Hospital of Jilin University from 2006 to 2020. Patients were grouped according to age: below 60 years (non-elderly group, n = 5923) and at least 60 years (elderly group, n = 1199). The clinical and pathological characteristics of renal biopsy patients in the groups were analyzed using the t-test and chi-square test. RESULTS: Compared with the non-elderly group, the elderly group had significantly fewer patients with primary glomerulonephritis, but more patients with tubulointerstitial disorders (p < .05). The incidence of IgA nephropathy, mesangial proliferative glomerulonephritis, and lupus nephritis was significantly lower in elderly patients than in non-elderly patients. The incidence of membranous nephropathy, membranoproliferative glomerulonephritis, diabetic nephropathy, hypertensive nephropathy, systemic vasculitis-associated renal damage, and amyloid nephropathy was significantly higher in elderly patients than in non-elderly patients (p < .05). The incidence of perinephric hematoma (≥4 cm2) in elderly patients with renal biopsy was lower than that in non-elderly patients. We noted that 79.9% of primary glomerulonephritis patients who received immunosuppressive therapy showed a remission rate of 83.5%. CONCLUSION: The spectrum of kidney disease in the elderly is different from that in the younger population.

Asunto(s)

Biopsia , Glomerulonefritis/epidemiología , Hipertensión Renal/epidemiología , Nefritis/epidemiología , Anciano , Anciano de 80 o más Años , China/epidemiología , Nefropatías Diabéticas/epidemiología , Nefropatías Diabéticas/patología , Femenino , Glomerulonefritis/patología , Glomerulonefritis por IGA/epidemiología , Glomerulonefritis por IGA/patología , Glomerulonefritis Membranoproliferativa/epidemiología , Glomerulonefritis Membranoproliferativa/patología , Glomerulonefritis Membranosa/epidemiología , Glomerulonefritis Membranosa/patología , Humanos , Hipertensión Renal/patología , Incidencia , Riñón/patología , Nefritis Lúpica/epidemiología , Nefritis Lúpica/patología , Masculino , Persona de Mediana Edad , Nefritis/patología , Estudios Retrospectivos

RESUMEN

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m2, and 24-hour proteinuria level of 0.5-3.0 g, were recruited in 41 hospitals across 19 provinces in China and were randomly divided into five groups: SYKFT, losartan potassium 50 mg or 100 mg, SYKFT plus losartan potassium 50 mg or 100 mg. MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER: NCT02063100 on ClinicalTrials.gov.

Asunto(s)

Medicamentos Herbarios Chinos , Glomerulonefritis , China , Método Doble Ciego , Medicamentos Herbarios Chinos/efectos adversos , Glomerulonefritis/tratamiento farmacológico , Humanos , Medicamentos sin Prescripción , Comprimidos , Resultado del Tratamiento

RESUMEN

BACKGROUND AND OBJECTIVES: Glomerulonephritis (GN) is one of the main causes of chronic terminal kidney disease; however, few studies assess its prognosis in dialysis. We analyze the survival and characteristics of patients on peritoneal dialysis (PD) with primary GN (PGN), and compare their results with other kidney patients. METHODS: This prospective observational study took place from 1995 to 2014. We included all incident patients who were initiated on the technique in the Levante registry. Data were transferred to an anonymized database in Access. Statistical analysis was performed using SPSS software (version 19.0). RESULTS: The study included 2243 patients, with GN representing the main cause of primary kidney disease (21,5%). IgA nephropathy was the most frequent histologically confirmed form of PGN. Compared with the rest of the sample, patients with PGN were more often men (65% vs 58%, p = .004), and they were on average younger (48 years vs 55 years, p < .001). They also had fewer comorbidities and a higher rate of inclusion on the waitlist for a kidney transplant (87 vs 63%, p < .001). Patients with PGN also had more transplants (48,9%, p < .001), and this was the most frequent reason for stopping PD; beyond that, their peritonitis mean rate was lower (0,34 vs 0,45 episodes/patient-year, p < .001). Technique survival was 90,6% at one year, 71,7% at 3 years, and 59,0% at 5 years (median 76,8 months); there were no differences between groups. Survival was 94,9% at one year, 80,1% at 3 years, and 63,7% at 5 years (median 90,7 months). Patients with PGN showed better mean survival than patients with other kidney pathologies (153,5 months [95% IC: 137,0-169,9] vs 110,3 months [95% CI: 100,8-119,7], p < .001). In the multivariable analysis, the main negative risk factor influencing technique survival was a higher peritoneal transport (p = .018). Factors with a negative influence on mortality were being older (p < .001) and having any comorbidity, mainly diabetes and liver disease (p < .001). By contrast, protective survival factors were inclusion on the transplant waitlist and a higher baseline residual renal function (p = .001). CONCLUSIONS: PD has several advantages as a first dialytic treatment, and our results suggest that it is an excellent technique to manage patients with PGN while they await a kidney transplant.

RESUMEN

BACKGROUND AND OBJECTIVES: Glomerulonephritis (GN) is one of the main causes of chronic terminal kidney disease; however, few studies assess its prognosis in dialysis. We analyze the survival and characteristics of patients on peritoneal dialysis (PD) with primary GN (PGN), and compare their results with other kidney patients. METHODS: This prospective observational study took place from 1995 to 2014. We included all incident patients who were initiated on the technique in the Levante registry. Data were transferred to an anonymized database in Access. Statistical analysis was performed using SPSS software (version 19.0). RESULTS: The study included 2,243 patients, with GN representing the main cause of primary kidney disease (21,5%). IgA nephropathy was the most frequent histologically confirmed form of PGN. Compared with the rest of the sample, patients with PGN were more often men (65% vs 58%, P=.004), and they were on average younger (48 years vs 55 years, P<.001). They also had fewer comorbidities and a higher rate of inclusion on the waitlist for a kidney transplant (87 vs 63%, P<.001). Patients with PGN also had more transplants (48,9%, P<.001), and this was the most frequent reason for stopping PD; beyond that, their peritonitis mean rate was lower (0,34 vs 0,45 episodes/patient-year, P<.001). Technique survival was 90,6% at one year, 71,7% at 3 years, and 59,0% at 5 years (median 76,8 months); there were no differences between groups. Survival was 94,9% at one year, 80,1% at 3 years, and 63,7% at 5 years (median 90,7 months). Patients with PGN showed better mean survival than patients with other kidney pathologies (153,5 months [95% IC: 137,0 to 169,9] vs 110,3 months [95% CI: 100,8 to 119,7], P<.001). In the multivariable analysis, the main negative risk factor influencing technique survival was a higher peritoneal transport (P=.018). Factors with a negative influence on mortality were being older (P <.001) and having any comorbidity, mainly diabetes and liver disease (P <.001). By contrast, protective survival factors were inclusion on the transplant waitlist and a higher baseline residual renal function (P=.001). CONCLUSIONS: PD has several advantages as a first dialytic treatment, and our results suggest that it is an excellent technique to manage patients with PGN while they await a kidney transplant.

RESUMEN

Primary glomerulonephritis can recur after kidney transplantation and may jeopardize the survival of the renal allograft. The risks of living-related kidney transplantation remain controversial in this group of patients. Living related transplantation offers potentially better HLA matching, therefore improve the long-term graft survival. However, the concern for increased rates of recurrence of the primary glomerulonephritis in the transplanted kidney from living related donors complicates the selection of donors. With the recent dramatic rise in the use of paired kidney exchange, there is now often the option of having a living related donor donate through a paired exchange. This raises the question of whether patients with primary glomerulonephritis should receive living donor kidneys through paired kidney exchange programs to obtain the benefits of a living donor kidney transplant while also reducing the risk of recurrent glomerulonephritis. Our review of the literature suggests that although the recurrence of primary glomerulonephritis occurs more often when donation occurs from a living related donor as compared to an unrelated donor, the graft survival advantage of living related donation is generally maintained despite the recurrence. We suggest that despite the increased risk of recurrence, living related donation should not be avoided in patients with primary glomerulonephritis as the cause of their end-stage renal disease.

Asunto(s)

Glomerulonefritis , Trasplante de Riñón , Glomerulonefritis/epidemiología , Supervivencia de Injerto , Humanos , Trasplante de Riñón/efectos adversos , Donadores Vivos , Recurrencia , Sistema de Registros , Donante no Emparentado

RESUMEN

BACKGROUND@#Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease.@*OBJECTIVE@#This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m@*MAIN OUTCOME MEASURES@#The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment.@*RESULTS@#A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group.@*CONCLUSION@#SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone.@*TRIAL REGISTRATION NUMBER@#NCT02063100 on ClinicalTrials.gov.

RESUMEN

OBJECTIVE: To identify serum microRNAs (miRNAs) as potential non-invasive biomarkers for patients with chronic kidney disease (CKD). METHODS: We collected serum samples from healthy controls, CKD stage 1 (CKD1), and stage 5 (CKD5) patients with primary glomerulonephritis (GN), screened differentially expressed miRNAs (DEMs) using next-generation sequencing (NGS), and confirmed the sequencing data using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RESULTS: We identified 20 and 42 DEMs in the CKD1 and CKD5 patients compared with the controls, respectively, and 70 DEMs in the CKD5 compared with the CKD1 patients. The qRT-PCR results showed that miR-483-5p was up-regulated in the CKD1 and CKD5 patients compared with controls (fold change = 2.56 and 18.77, respectively). miR-363-3p was down-regulated in the CKD5 patients compared with the controls and CKD1 patients (fold change = 0.27 and 0.48, respectively). CONCLUSION: We identified a genome-wide serum miRNA expression profile in CKD patients, and serum miR-483-5p and miR-363-3p may act as potential diagnostic biomarkers for CKD.

Asunto(s)

MicroARNs , Insuficiencia Renal Crónica , Biomarcadores , Biomarcadores de Tumor , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , MicroARNs/genética , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/genética

RESUMEN

INTRODUCTION: The frequency of glomerulonephritis (GN) is reported to be changing in the world over the past four decades. Few studies arise from the western region of Saudi Arabia. AIMS: The aim of this study was to address the frequency of primary GN (1ry GN) and secondary GN (2ry GN) over a period of 26 years in the western region of Saudi Arabia and compare to previous data from other regions of the country. SUBJECTS AND METHODS: The records of adult renal biopsies, 448 1ry GN and 263 2ry GN, are analyzed. Frequencies of GN subtypes are compared for period 1 (1988-19999) and period 2 (2000-2013). RESULTS: Postinfectious GN (PIGN) and minimal change disease (MCD) show significant changes (P ≤ 0.05). PIGN increased to 6.5% in period 2 from 0% in period 1. MCD decreased to 5.9% in period 2 from 13.5% in period 1. Membranous GN is the most common 1ry GN for both periods with similar percentages (23.8% and 24.2%, respectively). Focal segmental glomerulosclerosis (FSGSC) is the second in period 2 (23%); immunoglobulin A nephropathy at 9.6% became the third, and MCD is the last place instead of the fourth in period 1. Lupus nephritis is the most common 2ry GN. Pooled data from Saudi studies show FSGSC the most common 1ry GN in both periods. CONCLUSIONS: The western region of Saudi Arabia presents with a different 1ry GN pattern than the rest of the country that is likely attributed to its unique geographical and environmental characteristics.

RESUMEN

The kidney is often the target of immune system dysregulation in the context of primary or systemic disease. In particular, the glomerulus represents the anatomical entity most frequently involved, generally as the expression of inflammatory cell invasion or circulant or in situ immune-complex deposition. Glomerulonephritis is the most common clinical and pathological manifestation of this involvement. There are no universally accepted classifications for glomerulonephritis. However, recent advances in our understanding of the pathophysiological mechanisms suggest the assessment of immunological features, biomarkers, and genetic analysis. At the same time, more accurate and targeted therapies have been developed. Data on pediatric glomerulonephritis are scarce and often derived from adult studies. In this review, we update the current understanding of the etiologic events and genetic factors involved in the pathogenesis of pediatric immunologically mediated primitive forms of glomerulonephritis, together with the clinical spectrum and prognosis. Possible new therapeutic targets are also briefly discussed.

RESUMEN

BACKGROUND: Previous reports suggest initial presentation of IgA nephropathy (IgAN) in children is different from adults. No systematic comparison of clinical, biological, and histological childhood- and adult-onset IgAN is currently available. METHODS: We compared pediatric and adult clinical and histological characteristics at IgAN diagnosis. Data on 211 consecutive patients from two different centers in Paris (82 children, 129 adults) were reviewed. Kidney biopsies were scored for Oxford classification and podocytopathic (P1) features. RESULTS: We report higher eGFR at diagnosis in children compared to adults (89.5 vs. 64 ml/min/1.73 m2; p = 0.0001) but no difference in proteinuria. Histological analysis of kidney biopsy found higher proportions of mesangial (M1) and endocapillary (E1) hypercellularity in children compared with adults (M1 [80.7% vs. 27.9%, p = 0.0001]; E1 [71.3% vs. 30%, p = 0.0001]). Focal glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis ≥ 25% (T1), and P1 were more frequent in adults (S1 [81.5% vs. 61.3%, p = 0.0012], T1 [49.5% vs. 1.35%, p = 0.0001], P1 [33.8% vs. 16.4%, p = 0.008). Proteinuria associated with M1, E1, and C1 in children (M1, p = 0.0001; E1, p = 0.0005; C1, p = 0.0014) but S1, P1, and T1 in adults (S1, p = 0.0001; P1, p = 0.0001; T1, p = 0.001). After steroid treatment (41 children and 28 adults), proteinuria decreased in children (p < 0.001, follow-up 38 months) and adults (p < 0.001, follow-up 76.9 months), whereas eGFR remained stable in adults but increased significantly in children (90.6 to 110 ml/min/1.73m2). CONCLUSION: Proteinuria in children with IgAN is a marker of glomerular proliferative lesions whereas its presence in adults often reflects the presence of chronic lesions. This suggests the need for histological assessment.

Asunto(s)

Glomerulonefritis por IGA/diagnóstico , Glomeruloesclerosis Focal y Segmentaria/epidemiología , Glucocorticoides/administración & dosificación , Glomérulos Renales/patología , Proteinuria/diagnóstico , Adulto , Factores de Edad , Biopsia , Niño , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular/efectos de los fármacos , Tasa de Filtración Glomerular/fisiología , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/inmunología , Glomeruloesclerosis Focal y Segmentaria/diagnóstico , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/inmunología , Humanos , Glomérulos Renales/efectos de los fármacos , Glomérulos Renales/inmunología , Masculino , Proteinuria/tratamiento farmacológico , Proteinuria/inmunología , Proteinuria/orina , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento

RESUMEN

BACKGROUND: The treatment of most glomerulonephritides is still based on a combination of an oral corticosteroid and an alkylating agent, with favorable outcomes, but with serious side effects. The objective of this study was to reduce the cumulative corticosteroid dose in patients with high risk of corticosteroid-related adverse events by replacing daily oral corticosteroids with intravenous (iv) methylprednisolone pulses, associated with monthly pulse i.v. cyclophosphamide (according to KDIGO guidelines) in patients with glomerulonephritis. METHODS: This was a retrospective cohort study conducted at a single nephrology centre. In the course of a 6-month run-in phase, all the patients received non-immunosuppressive pathogenic treatment. High-risk patients, who still had urinary protein excretion of at least 3.5 g per day at the end of these 6 months, received a combination of corticosteroids and cyclophosphamide. Patients were divided in two groups: group 1 (23 patients)-included patients with high risk of corticosteroid-related adverse events received monthly methylprednisolone 1 g/day, 3 days and i.v. cyclophosphamide for 6 months, and group 2 (84 patients)-received oral corticosteroids (as per KDIGO recommended dose) and i.v. cyclophosphamide. The primary outcome-time to a combined end-point of doubling of serum creatinine, ESRD, need for chronic renal replacement therapy or death; secondary outcomes: complete remission [proteinuria < 0.3 g per 24 h (urinary protein-creatinine rate < 300 mg/g [< 30 mg/mmol]]; partial remission (proteinuria > 0.3 but < 3.5 g per 24 h or a decrease in proteinuria by at least 50% from the initial value) and adverse events. RESULTS: At 6 months, there was no difference in the primary composite end-point: 8.7% patients from the group 1 and 20.2% patients from the group 2 (P = 0.199) reached this end-point. Similar data were also recorded at 12 months. Secondary end-points were also similar between treatment groups. More patients receiving oral corticosteroids experienced infections, but without statistical significance. CONCLUSION: Our data indicate that low i.v. dose corticosteroids and cyclophosphamide administered monthly in patients with high risk of corticosteroid-related adverse events and primary glomerulonephritis are equally effective, with fewer metabolic disorders and infections.

Asunto(s)

Ciclofosfamida/administración & dosificación , Glomerulonefritis/tratamiento farmacológico , Glucocorticoides/administración & dosificación , Inmunosupresores/administración & dosificación , Metilprednisolona/administración & dosificación , Administración Intravenosa , Adulto , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos

RESUMEN

RATIONALE & OBJECTIVE: Immunoglobulin A nephropathy (IgAN) is common worldwide and has heterogeneous phenotypes. Predicting long-term outcomes and stratifying risk are important for clinical decision making and designing future clinical trials. STUDY DESIGN: Multicenter retrospective cohort study of 2,047 patients with IgAN. SETTING & PARTICIPANTS: Derivation and validation cohorts composed of 1,022 Chinese patients with IgAN from a single center and 1,025 patients with IgAN from 18 renal centers, respectively. PREDICTORS: 36 characteristics, including demographic, clinical, and pathologic variables. OUTCOMES: Combined event of end-stage kidney disease or 50% reduction in estimated glomerular filtration rate within 5 years after diagnostic kidney biopsy. ANALYTICAL APPROACH: A gradient tree boosting method implemented in the eXtreme Gradient Boosting (XGBoost) system was used to select the 10 most important variables from 36 candidate variables. Stepwise Cox regression analysis was used to derive a simplified scoring scale model (SSM) based on these 10 variables. Model discrimination and calibration were assessed using the C statistic and Hosmer-Lemeshow test. Risk stratification of the SSM was evaluated using Kaplan-Meier analysis. RESULTS: In the derivation and validation cohorts, 74 and 114 patients reached the outcome, respectively. XGBoost predicted the outcome with a C statistic of 0.84 (95% CI, 0.80-0.88) for the validation cohort. The SSM included 3 variables: urine protein excretion, global sclerosis, and tubular atrophy/interstitial fibrosis. Using Kaplan-Meier analysis, the SSM identified significant risk stratification (P < 0.001). LIMITATIONS: Retrospective study design, application for other ethnic groups needs to be verified. CONCLUSIONS: A prediction model using routinely available characteristics and based on the combination of a machine learning algorithm and survival analysis can stratify risk for kidney disease progression in the setting of IgAN. An online calculator, the Nanjing IgAN Risk Stratification System, permits easy implementation of this model.

Asunto(s)

Glomerulonefritis por IGA/epidemiología , Adulto , Estudios de Cohortes , Femenino , Glomerulonefritis por IGA/complicaciones , Humanos , Fallo Renal Crónico/etiología , Masculino , Pronóstico , Estudios Retrospectivos , Medición de Riesgo/métodos