Validation of a Histologic Scoring Index for C3 Glomerulopathy.

RATIONALE & OBJECTIVE: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population. STUDY DESIGN: Multicenter, retrospective cohort study. SETTING & PARTICIPANTS: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). PREDICTORS: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score. OUTCOME: Time to kidney failure. ANALYTICAL APPROACH: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines. RESULTS: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure. LIMITATIONS: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding. CONCLUSIONS: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.

IgA Nephropathy in Elderly Patients.

BACKGROUND AND OBJECTIVES: Some studies suggest that the incidence of IgA nephropathy is increasing in older adults, but there is a lack of information about the epidemiology and behavior of the disease in that age group. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this retrospective multicentric study, we analyzed the incidence, forms of presentation, clinical and histologic characteristics, treatments received, and outcomes in a cohort of 151 patients ≥65 years old with biopsy-proven IgA nephropathy diagnosed between 1990 and 2015. The main outcome was a composite end point of kidney replacement therapy or death before kidney replacement therapy. RESULTS: We found a significant increase in the diagnosis of IgA nephropathy over time from six patients in 1990-1995 to 62 in 2011-2015 (P value for trend =0.03). After asymptomatic urinary abnormalities (84 patients; 55%), AKI was the most common form of presentation (61 patients; 40%). Within the latter, 53 (86%) patients presented with hematuria-related AKI (gross hematuria and tubular necrosis associated with erythrocyte casts as the most important lesions in kidney biopsy), and eight patients presented with crescentic IgA nephropathy. Six (4%) patients presented with nephrotic syndrome. Among hematuria-related AKI, 18 (34%) patients were receiving oral anticoagulants, and this proportion rose to 42% among the 34 patients older than 72 years old who presented with hematuria-related AKI. For the whole cohort, survival rates without the composite end point were 74%, 48%, and 26% at 1, 2, and 5 years, respectively. Age, serum creatinine at presentation, and the degree of interstitial fibrosis in kidney biopsy were risk factors significantly associated with the outcome, whereas treatment with renin-angiotensin-aldosterone blockers was associated with a lower risk. Immunosuppressive treatments were not significantly associated with the outcome. CONCLUSIONS: The diagnosis of IgA nephropathy among older adults in Spain has progressively increased in recent years, and anticoagulant therapy may be partially responsible for this trend. Prognosis was poor. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_07_16_CJASNPodcast_19_08_.mp3.

Long-term outcomes of IgA nephropathy presenting with minimal or no proteinuria.

The long-term outcome of patients with IgA nephropathy who present with normal renal function, microscopic hematuria, and minimal or no proteinuria is not well described. Here, we studied 141 Caucasian patients with biopsy-proven IgA nephropathy who had minor abnormalities at presentation and a median follow-up of 108 months. None of the patients received corticosteroids or immunosuppressants. We reviewed renal biopsies using the Oxford classification criteria. In this sample, 46 (32%) patients had mesangial proliferation, whereas endocapillary proliferation, focal glomerulosclerosis, and tubulointerstitial abnormalities were uncommon. Serum creatinine increases >50% and >100% were observed in five (3.5%) patients and one (0.7%) patient, respectively; no patients developed ESRD. After 10, 15, and 20 years, 96.7%, 91.9%, and 91.9% of patients maintained serum creatinine values less than a 50% increase, respectively. Using Cox proportional hazards regression, the presence of segmental glomerulosclerosis was the only factor that significantly associated with a >50% increase in serum creatinine. Clinical remission occurred in 53 (37.5%) patients after a median of 48 months. Proteinuria>0.5 and >1.0 g/24 h developed in 21 (14.9%) and 6 (4.2%) patients, respectively. Median proteinuria at the end of follow-up was 0.1 g/24 h, with 41 (29.1%) patients having no proteinuria. At presentation, 23 (16.3%) patients were hypertensive compared with 30 (21.3%) patients at the end of follow-up; 59 (41.8%) patients were treated with renin-angiotensin blockers because of hypertension or increasing proteinuria. In summary, the long-term prognosis for Caucasian patients with IgA nephropathy who present with minor urinary abnormalities and normal renal function is excellent.

Focal segmental glomerulosclerosis due to a relapsing non-Hodgkin's lymphoma diagnosed by positron emission tomography.

Glomerulonephritis rarely appears associated with Hodgkin's disease or non-Hodgkin's lymphoma (NHL). We present a patient with a relapse of a non-Hodgkin's lymphoma which first presented as nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS). This case report discusses the unusual association of non-Hodgkin's lymphoma and focal segmental glomerulosclerosis, as well as the crucial role of positron emission tomography in detecting the relapsing lymphoma.

Pathogenic significance of hypertrophic mesothelial cells in peritoneal effluent and ex vivo culture.

The presence of hypertrophic mesothelial cells (HMCs) in peritoneal effluent (PE) has been considered a possible marker for peritoneal sclerosis. We conducted the present study to evaluate if the presence of HMCs in PE or in culture was related to peritoneal function alterations or to the development of sclerosing peritonitis. We prospectively studied 32 new peritoneal dialysis (PD)patients every 4 months, determining the presence of HMCs in culture (completing 129 studies in total). We isolated mesothelial cells from nocturnal PE and cultured them ex vivo in T-25 flasks. Cell morphology was estimated using the May-Grünwald/Giemsa method. We also examined the histories of a large patient group to determine HMCs directly in PE, and we evaluated 4 of those patients (6%) who showed persistent HMCs. In 10 of 32 prospectively studied patients, we found HMCs during the culture phase. The cells appeared in the first evaluation in 4 patients and in subsequent cultures in the remaining 6 patients. Ultrafiltration (UF) and solute transport capacity in the 10 patients were similar to those of patients who did not show HMCs. Demographic parameters were not different between the two groups. None of the prospectively studied patients showed any clinical or peritoneal functional abnormality during the study. Cultures performed after the observation of HMCs showed very poor growth capacity. The evolution of the 4 patients in the historic group occurred as follows: We 1 patient transferred to hemodialysis 2 years after the observation of HMCs. 1 patient died of an unrelated cause after 1 year on PD. 1 patient received a successful kidney graft 5 years after the observation of HMCs. 1 patient developed type I UF failure 10 years after the first observation.