Increased prevalence of Kidney cysts in individuals carrying heterozygous COL4A3 or COL4A4 pathogenic variants.

BACKGROUND: Clinical variability among individuals with heterozygous pathogenic/likely pathogenic (P/LP) variants in the COL4A3/COL4A4 genes (also called autosomal dominant Alport syndrome or COL4A3/COL4A4 related disorder) is huge; many individuals are asymptomatic or show microhematuria, while others may develop proteinuria and chronic kidney disease (CKD). The prevalence of simple kidney cysts (KC) in the general population varies according to age, and patients with advanced CKD are prone to have them. A possible association between heterozygous COL4A3, COL4A4, and COL4A5 P/LP variants and KC has been described in small cohorts. The presence of KC in a multicenter cohort of individuals with heterozygous P/LP variants in the COL4A3/COL4A4 genes is assessed in this study. METHODS: We evaluated the presence of KC by ultrasound in 157 individuals with P/LP variants in COL4A3 (40.7%) or COL4A4 (53.5%) without kidney replacement therapy. The association between presence of KC and age, proteinuria, eGFR, and causative gene was analyzed. Prevalence of KC was compared with historical case series in the general population. RESULTS: Half of the individuals with P/LP variants in COL4A3/COL4A4 showed KC, which is a significantly higher percentage than in the general population. Only 3.8% (6/157) had cystic nephromegaly. Age and eGFR showed an association with the presence of KC (p<0.001). No association was found between KC and proteinuria, sex, or causative gene. CONCLUSIONS: Individuals with COL4A3/COL4A4 P/LP variants are prone to develop KC more frequently than the general population, and their presence is related to age and to eGFR. Neither proteinuria, sex nor the causative gene influences the presence of KC in these individuals.

Autosomal Dominant Polycystic Kidney Disease: Clinical Assessment of Rapid Progression.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) causes the development of renal cysts and leads to a decline in renal function. Limited guidance exists in clinical practice on the use of tolvaptan. A decision algorithm from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Working Groups of Inherited Kidney Disorders and European Renal Best Practice (WGIKD/ERBP) has been proposed to identify candidates for tolvaptan treatment; however, this algorithm has not been assessed in clinical practice. METHODS: Eighteen-month cross-sectional, unicenter, observational study assessing 305 consecutive ADPKD patients. The ERA-EDTA WGIKD/ERBP algorithm with a stepwise approach was used to assess rapid progression (RP). Subsequently, expanded criteria based on the REPRISE trial were applied to evaluate the -impact of extended age (≤55 years) and estimated glomerular filtration rate (eGFR; ≥25 mL/min/1.73 m2). RESULTS: Historical eGFR decline, indicative of RP, was fulfilled in 26% of 73 patients who were candidates for RP assessment, mostly aged 31-55 years. Further tests including ultrasound and MRI measurements of kidney volume plus genetic testing enabled the evaluation of the remaining patients. Overall, 15.7% of patients met the criteria for rapid or likely RP using the algorithm, and the percentage increased to 27% when extending age and eGFR. CONCLUSIONS: The ERA-EDTA WGIKD/ERBP algorithm provides a valuable means of identifying in routine clinical practice patients who may be eligible for treatment with tolvaptan. The impact of a new threshold for age and eGFR may increase the percentage of patients to be treated.

Change from three times a week on-line hemodiafiltration to short daily on-line hemodiafiltration.

BACKGROUND: Daily dialysis has shown excellent clinical results because a higher frequency of dialysis is more physiologic. On-line hemodiafiltration (OL-HDF) is a HDF technique that combines diffusion with high convection in which the dialysis fluid itself is used as a reinfusion solution. The aim of this study was to demonstrate the beneficial effect of the more effective dialysis schedule (daily dialysis) with the dialysis modality that offers the highest uremic toxin removal (on-line HDF). METHODS: Eight patients, six males and two females, on standard 4 to 5 hours three times a week OL-HDF (S-OL-HDF) were switched to daily OL-HDF (D-OL-HDF) 2 to 21/2 hours six times per week. Dialysis parameters were identical during both periods and only frequency and dialysis time of each session were changed. Tolerance, uremic toxin removal, urea kinetics, biochemical and anemia profiles, blood pressure, and left ventricular hypertrophy were evaluated. RESULTS: D-OL-HDF was well accepted and tolerated. The disappearance of postdialysis fatigue was rapidly reported by patients. Patients mantained the same [time average concentration (TAC) and weekly single-pool Kt/V (spKt/V)] throughout the study. However, equivalent renal urea clearance (EKR), standard Kt/V and weekly urea reduction ratio (URR) were increased during D-OL-HDF. Weekly urea, creatinine, osteocalcin, beta2-microglobulin, myoglobin, and prolactin reduction ratios were improved with D-OL-HDF. There was a significant decrease in predialysis plasma levels of urea, creatinine, acid uric, beta2-microglobulin and homocysteine over 6 months. Phosphate binders were reduced and antihypertensive drugs were stopped. A 30% regression of left ventricular mass was observed. CONCLUSION: The change from S-OL-HDF to D-OL-HDF was well tolerated. Disappearance of postdialysis fatigue, better dialysis adequacy, a higher removal of middle and large molecules, a reduction of phosphate binders, improvement of status nutritional, and an important reduction of cardiovascular risk factors were observed.