Expression of the kidney anion exchanger 1 affects WNK4 and SPAK phosphorylation and results in claudin-4 phosphorylation.

In the renal collecting ducts, chloride reabsorption occurs through both transcellular and paracellular pathways. Recent literature highlights a functional interplay between both pathways. We recently showed that in polarized inner medullary collecting duct cells, expression of the basolateral kidney anion exchanger 1 (kAE1) results in a decreased transepithelial electrical resistance (TEER), in a claudin-4 dependent pathway. Claudin-4 is a paracellular sodium blocker and chloride pore. Here, we show that kAE1 expression in mouse inner medullary collecting duct cells triggers WNK4, SPAK and claudin-4 phosphorylation. Expression of a functionally dead kAE1 E681Q mutant has no effect on phosphorylation of these proteins. Expression of a catalytically inactive WNK4 D321A or chloride-insensitive WNK4 L319F mutant abolishes kAE1 effect on TEER, supporting a contribution of WNK4 to the process. We propose that variations of the cytosolic pH and chloride concentration upon kAE1 expression alter WNK4 kinase activity and tight junction properties.

Conservative therapy is associated with worse clinical features and biochemical derangements than renal replacement therapy: a retrospective study in Kumasi, Ghana.

BACKGROUND: The incidence of end stage kidney disease (ESKD) is increasing in Ghana as with the rest of the world. This study compared the sociodemographic, diagnostic characteristics (clinical, biochemical and imaging) and clinical outcomes of ESKD patients who chose either renal replacement therapy (RRT) or conservative therapy as well as the factors that influenced their choice. METHODS: We retrospectively reviewed the records of 382 ESKD patient from 2006 to 2018. The data was collected from the Nephrology Clinic at the Komfo Anokye Teaching Hospital (KATH). Sociodemographic, diagnostic (clinical, biochemical and imaging) and therapeutic data were obtained, organized and analyzed with Statistical Package for the Social Sciences (SPSS). RESULTS: Of the 382 patients, 321 had conservative therapy whiles 61 had renal replacement therapy. The mean age of participants was 47.71 ± 16.10 years. Bipedal swelling (16.8%), fatigue (10.4%) and facial swelling (9.2%) were the major clinical features. Chronic glomerulonephritis (31.4%), hypertension (30.3%) and diabetes mellitus nephropathy (28.2%) were the most frequent predisposing conditions. Nifedipine (82.0%), bisoprolol (32.8%), aspirin (19.7%), ranitidine (26.2%), metformin (13.1%) and lasix (78.7%) were commonly used by the RRT patients than their conservative therapy counterparts. Compared to their RRT counterparts, patients on conservative therapy were more on irbesartan/lisinopril (57.9%) and sodium hydro carbonate (NaHCO3) (52.0%). Diastolic blood pressure (DBP) (p = 0.047), uremic gastritis (p = 0.007), anaemia, uraemia, haematuria and hyperkalaemia (p < 0.001) were more common in conservative therapy patients than RRT patients with RRT patients showing better corticomedullary differentiation (38.1% vs. 27.7%, p < 0.001) and normal echotexture (15.0% vs. 11.6%, p = 0.005). Age, gender, occupation and duration of illness were significantly associated with the decision to opt for conservative therapy. CONCLUSION: Patients on conservative therapy have worse clinical outcomes than their RRT counterparts. Early referrals to nephrologist as well as subsidized RRT should be targeted.

Abnormal Obesity Phenotype Is Associated with Reduced eGFR among Diabetes Mellitus and Hypertensive Patients in a Peri-Urban Community in Ghana.

Background: Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia due to obesity and defects in insulin action. Significant complications of DM include kidney disease due to its association with hypertension and obesity. Thus, the contribution of the various obesity phenotypes to the kidney impairment observed among hypertensive and diabetes mellitus patients is of major concern. Aim: The study assessed the association between obesity phenotypes and reduced glomerular filtration rate among diabetes mellitus and hypertensive patients. Methods: Three hundred and ten (310) adult patients diagnosed with type 2 diabetes mellitus, hypertension, or both who attended the Presbyterian Hospital, Dormaa Ahenkro, from October 2016 to March 2017 were recruited for the study. Blood samples were collected to analyze biochemical parameters (fasting blood glucose (FBG), lipid profile, and creatinine). Questionnaires were used to collect sociodemographic information, and anthropometrics were appropriately measured. The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation, and reduced eGFR was defined as eGFR <90 ml/min/1.73 m2. Results: The prevalence of metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically abnormal nonobese (MANO), and metabolically abnormal obese (MAO) phenotypes among the study participants was 30.65%, 4.50%, 52.90%, and 11.94%, respectively. The highest prevalence of reduced eGFR (29/37 (78.38%)) was seen among the MAO group. This was followed by the MANO, MHO, and MHNO with a reduced eGFR prevalence of 62.20%, 57.64%, and 37.89%, respectively. After normalization with MHNO, the reduced eGFR was 1.51, 1.64, and 2.06 times expressed in MHO, MANO, and MAO. For the total samples, when MHNO was maintained as a reference, reduced eGFR was significantly associated with MANO (aOR = 3.07 (95% CI = 1.76-5.35), P < 0.001) and MAO (aOR = 5.67 (95% CI = 2.66-17.27), P < 0.001) even after adjusting for age, gender, smoking, and alcohol intake. This association was maintained among the female study participants when stratified by gender, and in addition, among the female participants, reduced eGFR was also associated with MHO (aOR = 4.19 (95% CI = 1.06-16.53), P=0.041). Conclusion: There is a high prevalence of abnormal metabolic phenotypes among diabetes mellitus patients, and these were significantly associated with reduced eGFR among our study participants.

Demographic, diagnostic and therapeutic characteristics of autosomal dominant polycystic kidney disease in Ghana.

BACKGROUND: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the commonest of the hereditary kidney diseases and mostly ensues in utero with signs delayed until after several decades. This study assessed the demographic, diagnostic (clinical and biochemical features) and therapeutic patterns among ADPKD patients who attended the nephrology unit of Komfo Anokye Teaching Hospital (KATH) from 2007 to 2018. METHODS: This cross-sectional retrospective analysis of ADPKD patient records was conducted at the nephrology unit of KATH in October 2020. The records of 82 ADPKD was used for this study. Demographic, clinical, biochemical, ultrasonographic and therapeutic data was obtained, organized and analyzed with Statistical Package for the Social Sciences (SPSS). RESULTS: ADPKD was most prevalent in people within the ages of 31-40 years (25.6 %), with a male (52.4 %) preponderance. The most common clinical features presented were flank pain (30.5 %) and bipedal swelling (18.3 %). Hypertension (42.7 %), urinary tract infections (UTIs) (19.5 %), and anemia (13.4 %) were the most common complications reported. Average level of HDL-c was higher in females (1.7) than in males (1.2) (p = 0.001). Hematuria (34 %) and proteinuria (66 %) were among the biochemical derangements presented. About 81.7 % had CKD at diagnosis with the majority in stages 1 (27.0 %), 3(23.2 %) and 5 (20.3 %). Poor corticomedullary differentiation was observed in 90.2 % of participants and increased echogenicity was observed in 89.0 % of the participants. Estimated GFR (eGFR) correlated positively with echotexture (r = 0.320, p = 0.005) and negatively with CMD (r= -0.303, p = 0.008). About 95.1 % of patients were on conservative therapy including: 73.2 %, 52.4 %, 22.0 %, 13.4 %, 8.5 % on Irebesartan/Lisinopril, Nifecard XL, Hydralazine, Methyldopa and Bisoprolol respectively for hypertension; 26.8 and 3.7 % on Gliclazide and Metformin respectively for Type 2 diabetes mellitus; 25.6 %, 24.4 and 18.3 % on CaCO3, fersolate and folic acid respectively as nutrient supplements with 4.9 % of participants on renal replacement therapy (RRT). CONCLUSIONS: ADPKD occurs in people aged ≥ 31 years with a higher male preponderance. Clinical features include flank and abdominal pain, bipedal swelling, headache, amongst others. Uremia, hematuria, proteinuria, decreased eGFR, were the common biochemical derangements reported with higher severity detected in men. The therapeutic interventions mostly involved conservative therapy to manage symptoms and other comorbid conditions and rarely renal replacement therapy (RRT).