ABSTRACT
Chronic Kidney Disease is an increasing worldwide disease affecting millions across races and continents globally. Several gene variants, modifiable life style, metabolic disorders, environmental factors, amongst others have been reported to be involved in the pathways driving the pathogenesis of the disease. The association of UMOD gene mutations with autosomal dominant tubulointerstitial kidney disease which can lead to CKD has been reported elsewhere. The need to know whether such gene mutation is responsible for CKD progression in Nigeria is desirable. A total of 184 randomized CKD patients attending renal clinic at the Central Hospital, Benin City, and 80 healthy control subjects were recruited for this study. A well-structured questionnaire was used to obtain data on socio-demography. Blood specimen collected from each patient was used for the determination of Full blood count, Renal function test, Lipid profile, Blood Glucose, Glycated haemoglobin (HBA1C), thyroid stimulating hormone, triiodothyronine, free triiodothyronine, thyroxine, free thyroxine, thyroid peroxidase antibody, thyroid globulin antibody, Deiodinase enzyme Type 1(D1) and serum Uromodulin were determined using standard methods. PCR was used for UMOD gene sequencing. SPINA GD and SPINA GT were calculated while the allostatic load score of each patient was determined with Z-score using biomarkers from immune response, metabolic and cardiovascular parameters. The CKD was classified using MDRD formula, but no stage 1 was detected among the study group. Stage 2, were 2 patients, stage 3 were 22, stage 4 were 47 while stage 5 were 113. A total of 22 samples comprising of 17 CKD patients were selected from the different stages of the disease and 5 controls were sequenced for UMOD gene mutation. Of the 17 CKD subjects sequenced, 6(32%) patients had mutations, among patients stage 3, stage 4 and stage 5. There were 4 novel mutations observed; 3 Missense mutations, L599S, R601P, S602Y and 1 silent mutation V600V. Serum uromodulin concentration (ng/mL) was significantly lower (p<0.001) among CKD than control irrespective of whether there was mutation or not. Serum uromodulin concentration decreased significantly with CKD progression p<0.0001, however, the level of serum uromodulin in CKD stage 4 did not differ significantly from CKD stage 5. Serum uromodulin concentration was not associated with CKD patients with hypertension, diabetes and glomerulonephritis (p>0.05). However, the mean concentration of serum uromodulin among CKD with polycystic kidney disease was significantly lower than CKD without polycystic kidney disease (p<0.01). Thyroid dysfunctions observed among the CKD patients were clinical hyperthyroidism 1(0.54%), non-thyroidal illness 78(42.4%), clinical hypothyroidism 11(6.0%), sub-clinical hyperthyroidism 3(1.60%), and sub-clinical hypothyroidism 11(6.0%), while 80(43.5%) were euthyroid. SPINA GD of CKD patients was not significantly different when compared with controls whereas, SPINA GT was significantly higher (p<0.01) among CKD patients than controls. However, neither SPINA GD nor SPINA GT was associated with CKD progression (p>0.05). Allostatic load score of CKD patients was significantly higher (p<0.01) than the control, but not with CKD progression. The total white blood cell, platelet count, percentage neutrophil count, RDW-SD, RDW-CV and PDW were significantly higher (p<0.05) among CKD patients than controls. Conversely, red blood cell count, haemoglobin, packed cell volume, mean cell haemoglobin, mean cell haemoglobin concentration and percentage lymphocyte count were significantly lower (p<0.01) among CKD patients than controls. Serum urea and creatinine, triglyceride, LDL-C and HBA1C were significantly higher (p<0.01) while HDL-C was lower among CKD patients than controls. In conclusion, novel UMOD gene variants were identified among CKD patients in Benin City, serum uromodulin levels were lower in CKD and correlated with disease progression. Thyroid gland dysfunctions were associated with (14.1%) CKD patients while non-thyroidal illness (42.4%) and euthyroid (43.5%) were observed. Allostatic load score was higher in CKD patients indicating a cumulative burden of chronic stress resulting from several physiological systems within patients with CKD. It also indicates reduced longevity, accelerated aging and weakened health.
