Genetic testing in focal segmental glomerulosclerosis: in whom and when?

Background: Genetic causes are increasingly recognized in patients with focal segmental glomerulosclerosis (FSGS), but it remains unclear which patients should undergo genetic study. Our objective was to determine the frequency and distribution of genetic variants in steroid-resistant nephrotic syndrome FSGS (SRNS-FSGS) and in FSGS of undetermined cause (FSGS-UC). Methods: We performed targeted exome sequencing of 84 genes associated with glomerulopathy in patients with adult-onset SRNS-FSGS or FSGS-UC after ruling out secondary causes. Results: Seventy-six patients met the study criteria; 24 presented with SRNS-FSGS and 52 with FSGS-UC. We detected FSGS-related disease-causing variants in 27/76 patients (35.5%). There were no differences between genetic and non-genetic causes in age, proteinuria, glomerular filtration rate, serum albumin, body mass index, hypertension, diabetes or family history. Hematuria was more prevalent among patients with genetic causes. We found 19 pathogenic variants in COL4A3-5 genes in 16 (29.3%) patients. NPHS2 mutations were identified in 6 (16.2%) patients. The remaining cases had variants affecting INF2, OCRL, ACTN4 genes or APOL1 high-risk alleles. FSGS-related genetic variants were more common in SRNS-FSGS than in FSGS-UC (41.7% vs 32.7%). Four SRNS-FSGS patients presented with NPHS2 disease-causing variants. COL4A variants were the most prevalent finding in FSGS-UC patients, with 12 patients carrying disease-causing variants in these genes. Conclusions: FSGS-related variants were detected in a substantial number of patients with SRNS-FSGS or FSGS-UC, regardless of age of onset of disease or the patient's family history. In our experience, genetic testing should be performed in routine clinical practice for the diagnosis of this group of patients.

Anemia development and cardiovascular risk management in nonanemic stage 3 chronic kidney disease.

BACKGROUND/AIM: There is little information on the development of anemia in the early stages of chronic kidney disease. The aim of this study was to analyze the onset of renal anemia in a cohort of initially nonanemic chronic kidney disease patients followed up in nephrology clinics. METHODS: This epidemiological, prospective, three-year, multicenter study enrolled patients aged 18-78 years with stage 3 chronic kidney disease without anemia. Interim analysis was performed on the data collected during the first 12 months. RESULTS: The study included 432 patients, average age 63.6 years (range 22-78 years, 70% male). The main etiologies of chronic kidney disease were glomerular (11.6%), interstitial (10.4%), vascular (29.4%), and diabetic (16.9%). The percentages of patients with comorbidities were 33.8% diabetes (2.5% type 1), 69% dyslipidemia, and 93% hypertension. During the first year, 12.4% of patients developed anemia. The chronic kidney disease progression rate was low: proteinuria was 0.46 +/- 0.8 g/24 h at one year versus 0.67 +/- 1.0 g/24 h at baseline. Diabetic patients showed a greater prevalence of previous cardiovascular events (50.0% vs. 24.5%) and worse control of some modifiable cardiovascular risk factors: smoking (13.4% vs. 8.6%), obesity (BMI > 30 kg/m(2), 33.6% vs. 25.3%), target blood pressure (<130/80 mmHg, 21.0% vs. 27.9%), and proteinuria (0.8 +/- 1.1 vs. 0.6 +/- 0.9 g/day). CONCLUSIONS: After one year, 12.4% of patients developed anemia. Diabetic patients had a higher cardiovascular risk and limited blood pressure control. The overall control of cardiovascular risk was unsatisfactory.

Effect of balance Solution on the Peritoneal Membrane in Automated Peritoneal Dialysis.

Interference of conventional peritoneal dialysis fluids (cPDFs) with peritoneal membrane cell functions may be attributed to the dialysis fluid's low pH, high glucose concentration, and/or the presence of glucose degradation products (GDPs), the last of which leads to higher levels of advanced glycation end-products (AGEs). It has been suggested that the peritoneal membrane might be better preserved by using biocompatible solutions, including cancer antigetn 125 (CA125). This prospective, open-label, multicentre, randomized, controlled, cross-over phase IV study compared the in vivo biocompatibility of a neutral-pH, low-GDP peritoneal dialysis (PD) solution (balance) with a cPDF in automated PD (APD) patients. Our study revealed a significantly increased appearance rate and concentration of CA125 in the peritoneal effluent of APD patients treated with the neutral-pH, low-GDP solution balance versus a conventional PD solution.

Peritoneal Dialysis Can Be an Option for Dominant Polycystic Kidney Disease: an Observational Study.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) has been considered a relative contraindication for peritoneal dialysis (PD), although there are few specific studies available. METHODS: A multicenter historical prospective matched-cohort study was conducted to describe the outcome of ADPKD patients who have chosen PD. All ADPKD patients starting PD (n = 106) between January 2003 and December 2010 and a control group (2 consecutive patients without ADPKD) were studied. Mortality, PD-technique failure, peritonitis, abdominal wall leaks and cyst infections were compared. RESULTS: Patients with ADPKD had similar age but less comorbidity at PD inclusion: Charlson comorbidity index (CCI) 4.3 (standard deviation [SD] 1.6) vs 5.3 (SD 2.5) p < 0.001, diabetes mellitus 5.7% vs 29.2%, p < 0.001 and previous cardiovascular events 10.4% vs 27.8%, p < 0.001. No differences were observed in clinical events that required transient transfer to hemodialysis, nor in peritoneal leakage episodes or delivered dialysis dose. The cyst infection rate was low (0.09 episodes per patient-year) and cyst infections were not associated to peritonitis episodes. Overall technique survival was similar in both groups. Permanent transfer to hemodialysis because of surgery or peritoneal leakage was more frequent in ADPKD. More ADPKD patients were included in the transplant waiting list (69.8 vs 58%, p = 0.04) but mean time to transplantation was similar (2.08 [1.69 - 2.47] years). The mortality rate was lower (2.5 vs 7.6 deaths/100 patient-year, p = 0.02) and the median patient survival was longer in ADPKD patients (6.04 [5.39 - 6.69] vs 5.57 [4.95 - 6.18] years, p = 0.024). CONCLUSION: Peritoneal dialysis is a suitable renal replacement therapy option for ADPKD patients.