Introduction: The correlation between genotype and phenotype is well described in ADPKD adults. PKD2 is milder than PKD1 disease, with end stage kidney disease (ESKD) occurring on average 20 years later, and patients with PKD1 truncating mutations having a more severe outcome than PKD1 non-truncating mutations. Still, large differences in outcome occur even within families carrying the same gene variation. Only a few cases series reported the genetic profile of severely affected ADPKD children and suggest an additional effect of hypomorphic genes. We therefore aim to analyse the geno-phenotype profile in a well characterized pediatric ADPKD cohort. Methods: Clinical, familial, biological and imaging data were collected longitudinally in children diagnosed with ADPKD. Genotypic analysis was done using a custom Agilent SureSelect gene panel containing 136 ciliopathy-associated genes, including PKD1 and PKD2. Mutations and/or variants identified were individually evaluated for pathogenicity. Results: 58 ADPKD children from 44 families were diagnosed at a mean (AE SD) age of 4.3 (AE5.0) years. ADPKD diagnosis was made in 33 children (57%) because of asymptomatic screening as requested by the family; 7 (12%) due to presenting symptoms (6 due to urinary tract infection and 1 due to post-traumatic macroscopic hematuria); 9 (15.5%) due to a coincidental finding of renal cysts on US performed for another reason and in 9 cases (15.5%) a prenatal diagnosis was performed. Twenty-nine children (50%) met the definition of very-early onset (VEO) disease.We identified pathogenic mutations in 100% of our patients, in which the prevalence of PKD1 truncating, PKD1 non-truncating, PKD2 and GANAB mutations was 74%, 21%, 3%, and 2%, respectively. Four cases (7%) were due to a de novo mutation. Interestingly, in 29 patients (50%) the germline mutation was the only identified mutation. However, in the rest of the subjects additional variants were identified in other ciliopathy-associated genes. In 13 cases (22%) the additional identified variants found in either the PKD, PMM2, HNF1B, DNAJC1, CEP290, NEK1, MKKS or PKHD1 genes were scored to have a potential phenotypic effect, which will be evaluated by continued follow-up of this cohort. Conclusions: We report the first large cohort of genotyped ADPKD children, including an extensive panel of ciliopathy genes next to the PKD genes. Interestingly, we found a high prevalence of additional and potentially modifying variants in this young population.
range), as appropriate. The student's T distribution was used to determine differences in the data collected between the two phases. P two-tail value <0.05 was considered statistically significant. Results were analyzed with the SPSS program. The study was approved by the IRB of the Fray Antonio Alcalde Civil Hospital, and registered at ClinicalTrials.gov (NCT03563898) Results: 51 of the 54 total sauna bath sessions were well tolerated, without side effects. Only in 3 sessions (5.5%) adverse effects were reported; transient dizziness in two cases, and skin burns in one patient with advanced diabetic neuropathy. A significant difference was observed between the recruitment phase and the intervention period in the over-hydration index (OH) (6.3 AE 1.2 Liters vs 5.5 AE 1.3 Liters, P = 0.03) and the over-hydration/extracellular water ratio (OH / ECW) (29 AE 3 % vs 26 AE 4 %, P = 0.05). We also observed a significance decrease in mean body weight (67.7 AE 3.7 kg vs 66.8 AE 3.8 kg, P = 0.001), diastolic blood pressure (92 AE 4 mmHg vs. 83 AE 4 mmHg, P = 0.007) and in the Global PSQI score (7.3 +-1.2 vs. 5.1 +-1, P = 0.008). Conclusions: Induced sweating by sauna bath can be a safe and effective alternative way to reduce fluid overload in peritoneal dialysis patients. Induced sweating could be useful in anuric patients and/or those with poor ultrafiltration when hemodialysis is not available. Because of the risk of skin burns, it should not be used in patients with peripheral neuropathy. Larger studies are needed to confirm our findings.
Glomerulonephritis (GN) is one of the major causes of chronic kidney disease (CKD) worldwide. It remains the leading cause of End Stage Kidney Disease (ESRD) in many developing countries including Nigeria with varying clinical course and histologic pattern. The clinical outcome and the degree of renal impairment observed in patients with glomerulonephritides is dependent on the type and extent of the histological lesion identified in the glomerulus and tubulointerstitium. Renal biopsy remains an important diagnostic tool in patients with glomerulonephritis with varying indications. This study is unique because the histologic features observed in the glomerulus and tubulo-interstitium were graded, scored and correlated with clinical as well as biochemical features. This will add to the body of knowledge on glomerulonephritides in this environment. The objectives of the study was to determine the grading and severity of histologic features observed in the glomerulus and tubulo-interstitium and to determine the relationship (if any) between clinical, biochemical and histologic features in adults with GN at OAUTHC, Ile-Ife. Methods: The study was a cross sectional hospital based study of seventy (70) consecutive adult patients with features of glomerulonephritis who presented at the nephrology and other clinics of OAUTHC Ile-Ife. Renal function was assessed and renal biopsy performed after obtaining written informed consent. The renal tissues obtained were subjected to light microscopy and immunoperoxidase staining with IgA, IgM, IgG and C 3 antibodies and the degree of involvement of glomeruli, tubules, interstitium and vessels were graded from 1 to 5 for the glomeruli and 1 to 3 for the tubulo-interstitium respectively according to severity. Total activity and total chronicity indices were collated and their association/correlation with clinical parameters assessed. Results: A total of seventy patients participated and completed the study. Three (3) patients had inadequate renal tissue for histologic diagnosis hence data analysis was based on the remaining sixty seven (67) patients. Statistically significant correlations were found between the interstitial scores for activity (interstitial oedema, interstitial infiltrate) with serum creatinine and GFR: interstitial oedema with serum creatinine (r¼0.35, p¼0.003) and GFR (r¼-0.38, p¼0.004); interstitial infiltrate with serum creatinine (r¼0.52, p<0.0002) and GFR (r¼-0.70, p¼0.002) and total activity index with serum creatinine (r¼0.60, p¼0.0001) and GFR (r¼-0.48, p ¼ 0.004). Statistically significant correlations was also seen between total chronicity index and test of renal function: total chronicity index with serum creatinine (r¼0.62, p¼0.001) and GFR (r¼-0.58, p<0.00001). Conclusions: Both activity and chronicity indices significantly influence renal function. The higher they are the lower the GFR and vice versa, this suggests aggressive management protocol for patients with higher indices. The histologic scoring system would assist in assessing the severity of t...
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