Severity and clinical causes of chronic kidney disease among outpatients from selected hospitals in Nairobi County, Kenya

Background: Chronic kidney disease (CKD) is a worldwide public health issue with high prevalence (8% and 16%) among adults. The severity of CKD and associated clinical features are less characterized in Kenya. We set to determine severity and clinical features of CKD among outpatient attendees in selected hospitals in Nairobi county.Methods: In this hospital based analytical cross-sectional study design, we collected data from Kenyatta National Hospital (KNH), Aga Khan University Hospital (AKUHN) and Mater Misericordiae Hospital. We recruited 336 adult CKD outpatients aged 18 years and above attending nephrology clinics between January and July, 2020 using a simple random sampling. A self-administered questionnaire was used to collect social-demographic data while data on severity and clinical features were retrieved from patient’s files of those who had given an informed consent. Descriptive and inferential statistics were performed using statistical package of social science version 26.0.Results: Majority of CKD patients (61.9%) had severe disease. Among patients with CKD, the following clinical features were statistically significant with severe disease; diabetic nephropathy (OR 3.43, 95% CI; 1.72, 5.67), glomerulonephritis (OR 2.52, 95% CI; 2.07, 4.05), hypertensive nephrosclerosis (OR 1.95, 95% CI; 1.87, 3.11), polycystic kidney disease (OR 1.26, 95% CI; 1.12, 2.61) and systemic lupus erythematosus (OR 1.16, 95% CI; 1.06, 1.39).Conclusions: Among outpatient attendees in Nairobi county, severe CKD is likely to be found in patients with diabetic nephropathy, glomerulonephritis, hypertensive nephrosclerosis, polycystic kidney disease and systemic lupus erythematosus. Therefore, the patients with these features need proper follow up and treatment to slow down progression of CKD to severe stages. However, more studies are need to be done to ascertain that the clinical features are responsible for severe CKD.

Study protocol and baseline characteristics of newly induced dialysis patients: a prospective multi-center cohort study with biological sample bank, the Ibaraki Dialysis Initiation Cohort Study (iDIC Study)

Background: Patients with end stage kidney disease (ESKD) face higher risk of life-threatening event including cardiovascular disease. Various risk factors have identified as an agent influencing their life prognosis. The study's purpose was to evaluate the risk factors related to the outcomes of Japanese patients with dialysis induction. In this brief report, we present this cohort study protocol and the baseline characteristics. Methods: Ibaraki Dialysis Initiation Cohort Study, iDIC Study, is a prospective multi-center cohort study in collaboration with 60 facilities in Ibaraki prefecture, Japan. We collected baseline data from clinical records, blood and urine samples in diabetic nephropathy, hypertensive nephrosclerosis and chronic glomerulonephritis Results: Sixty tertiary care institutions participated in the iDIC study, and 636 entries were analyzed. In this brief report, we present the baseline data of the entries in a comparison with the data of other similar cohort studies. Of the 636 patients, 424 were males and 212 were females. The average age was 67.4±13.1 years old. As the primary kidney disease, 327 cases (51.4%) were diagnosed as diabetic nephropathy, 101 cases (15.9%) as hypertensive nephrosclerosis, and 114 cases (17.9%) as chronic glomerulonephritis. The average serum creatinine value was 9.1 ± 2.9 mg/dL, and the average estimated glomerular filtration rate (eGFR) was 5.6 ± 1.8 mL/min/1.73m2. Conclusion: We presented the study protocols and baseline characteristics of iDIC Study. Regarding as clinical characteristics of newly induced dialysis patients, the same trend was observed in the other cohort studies. Another study is underway to explore prognostic factors based on the iDIC Study's findings.

Transfer RNA Fragments in the Kidney in Hypertension

Small noncoding RNAs (sncRNAs) are important regulators of gene expression. In contrast with well-studied microRNAs, transfer RNA-derived RNA fragments (tRFs) are a new class of sncRNAs that has not been studied in hypertension. This study aims to characterize renal tRFs and identify dysregulation and potential role of renal tRFs in hypertension. We analyzed sncRNA-sequencing and mRNA-sequencing data from the kidneys of Dahl salt-sensitive rats and sncRNA-sequencing data from kidney biopsy specimens from hypertensive nephrosclerosis patients. Over 300 tRFs were identified in the rat renal outer medulla, several of which were differentially expressed between rats with different levels of salt sensitivity or between rats on low- and high-salt diets. The number and abundance of these tRFs were comparable with those of well-known microRNAs. Multiple tRFs were potentially involved in the regulation of immune function, cell cycle, ion transport, and metabolic pathways based on an integrative analysis of sncRNA-sequencing and mRNA-sequencing data from the same set of rats. As a proof of concept, we experimentally validated the gene regulatory effect of a 3′-tRF (3′-tRF-ProTGG-19) that was dysregulated in both salt-induced hypertension in rats ( P =0.002) and hypertensive nephrosclerosis in humans ( P =1.7×10 −05 ). To our knowledge, our study represents the first characterization of tRFs in hypertension. These findings demonstrate the abundant expression of tRFs in human and rat kidneys and pave the way for studies to investigate novel roles of renal tRFs in the development of hypertension and renal injury.

Peritubular Capillary Rarefaction: An Underappreciated Regulator of CKD Progression

Peritubular capillary (PTC) rarefaction is commonly detected in chronic kidney disease (CKD) such as hypertensive nephrosclerosis and diabetic nephropathy. Moreover, PTC rarefaction prominently correlates with impaired kidney function and predicts the future development of end-stage renal disease in patients with CKD. However, it is still underappreciated that PTC rarefaction is a pivotal regulator of CKD progression, primarily because the molecular mechanisms of PTC rarefaction have not been well-elucidated. In addition to the established mechanisms (reduced proangiogenic factors and increased anti-angiogenic factors), recent studies discovered significant contribution of the following elements to PTC loss: (1) prompt susceptibility of PTC to injury, (2) impaired proliferation of PTC, (3) apoptosis/senescence of PTC, and (4) pericyte detachment from PTC. Mainly based on the recent and novel findings in basic research and clinical study, this review describes the roles of the above-mentioned elements in PTC loss and focuses on the major factors regulating PTC angiogenesis, the assessment of PTC rarefaction and its surrogate markers, and an overview of the possible therapeutic agents to mitigate PTC rarefaction during CKD progression. PTC rarefaction is not only a prominent histological characteristic of CKD but also a central driving force of CKD progression.

Hypertensive nephropathy: a major roadblock hindering the advance of precision nephrology

In the 2017 Annual Report of the ERA-EDTA Registry, hypertension continues to be the second or third most common cause of renal replacement therapy (RRT) in Europe, tied with glomerulonephritis. There is, however, one little issue: hypertension-induced end-stage renal disease (ESRD) might not exist at all as currently understood, that is, as hypertensive nephrosclerosis. In this regard, the incidence of RRT due to hypertensive nephropathy is related to the incidence of other causes of ESRD but not to the burden of hypertension per country. The current definition of hypertensive nephropathy is non-specific, outdated and only allows a delayed diagnosis by exclusion. It is not helpful that 80% of chronic kidney disease patients develop hypertension and kidney biopsy has no findings specific for hypertensive nephropathy. There is an urgent need to redefine the concept of hypertensive nephropathy with a clear and comprehensive set of criteria that at least should indicate how other nephropathies, including familial nephropathies, should be excluded. Correct causality assessment and aetiology-based therapy is a key to the progress of nephrology and it should no longer be accepted that ‘hypertensive nephropathy’ serves to disguise a suboptimal diagnostic workup. A diagnosis of nephropathy of unknown cause would be more honest when the full range of alternative aetiological diagnoses is not explored.

P0155CHARACTERISTICS OF HYPERTENSIVE NEPHROSCLEROSIS DIAGNOSED BY RENAL BIOPSY BASED ON 40-YEAR EXPERIENCE

Background and Aims Hypertensive nephrosclerosis (HT-N) is known as the second common cause of end stage renal disease (ESRD) in Korea as well as in other countries. However, the HT-N is assumed by clinical findings which are not well correlated to the pathologic findings. Therefore, we report the clinical characteristics of HT-N diagnosed by renal biopsy and compare the prognosis between patients with HT-N and hypertensive patients with focal segmental nephrosclerosis (FSGS) without pathologic HT-N. Method We enrolled 21,617 patients having native kidney biopsy for diagnosis of nephritis between 1979 and 2018, retrospectively. Among them, we selected 267 adult hypertensive patients with only HT-N and 984 hypertensive patients with FSGS without HT-N or other diagnoses (FSGS-HT). The estimated glomerular filtration rate (GFR) was calculated by original MDRD equation. The final outcomes were incidences of end stage renal disease (ESRD) and death. We matched blood pressures and GFR between two groups and analyzed the difference of outcomes within the matched cohort (mHT-N and mFSGS-HTN), also. Results The age of patients with HT-N was 49.5 ± 15.3 years at renal biopsy. There were 175 (65.5 %) men. Systolic blood pressure (SBP) was 139.1 ± 24.0 mmHg and diastolic blood pressure (DBP) was 83.7 ± 15.6 mmHg at renal biopsy. Levels of serum creatinine, GFR, and urine protein to creatinine ratio were 3.17 ± 3.05 mg/dl, 40.7 ± 32.5 ml/min/1.73 m2, and 2.277 ± 2.803 g/g cr, respectively. During follow-up period of 64.1 months (median), there were 52 (22.7%) patients progressed to ESRD and 8 (3.1%) patients were dead. Age, SBP, and hemoglobin were risk factors to mortality by Cox’s hazard proportional model adjusted with related factors to mortality. With increase of 10 mmHg in the level of SBP at renal biopsy, hazard ratio(HR) of mortality was increase by 1.645 folds (95% CI: 1.192-2.270, P=0.002). Presence of diabetes mellitus, serum albumin, and GFR were risk factors to incident ESRD. Compared to patients with FSGS-HT, patients with HT-N showed higher levels of SBP, DBP, and serum creatinine and lower levels of GFR, serum albumin, hemoglobin, and UPCR (all p-values <0.05), however, the risk of incident ESRD and mortality was not different. Therefore, we matched BP and GFR between groups and selected 235 patients in each group. The matched groups were not different in the values of age, SBP, DBP, and GFR. The risk of mortality was not different between groups (p-value =0.502), however, HR of incident ESRD was 1.558-fold higher (95% CI: 1.004-2.419, P=0.048) in mFSGS-HT compared to mHT-N by Cox’s hazard proportional model adjusted by factors related to ESRD. Conclusion Hypertensive nephrosclerosis was diagnosed in more advanced stage of CKD compared to hypertensive FSGS. Considering levels of GFR and SBP as risk factors to hard outcomes, we should consider early pathologic diagnosis for proteinuric and/or azotemic hypertensive patients and control blood pressures and renal dysfunction in more aggressive manners.

P15185 YEAR ALL-CAUSE MORTALITY ACCORDING TO PRIMARY RENAL DISEASE IN HEMODIALYSIS PATIENTS

Background and Aims The Korean Society of Nephrology (KSN) collected data of end-stage renal disease registry since 1985 and internet registry program was available since 2001. We explored the hypothesis that the 5-year mortality of hemodialysis patients was different depending on primary renal disease. Method From 2004 to 2015, in total, 32,163 patients starting hemodialysis were determined. The cause of primary renal disease were divided to diabetic nephropathy (49.9%, n=16,038), hypertensive nephrosclerosis (18.5%, n=5,958), histologically confirmed glomerulonephritis 3.3% (n=1,067), cystic kidney disease (2.0%, n=656) and the miscellaneous (26.3%, n=8,444). The miscellaneous included renal tuberculosis, interstitial nephritis, lupus nephritis, kidney tumor. Results The 5-year mortality of hemodialysis patients was 16.9 % (N=5,435) and ratio of unknown state was 24.9 % (N=7,996). The mortality of diabetic nephropathy, hypertensive nephrosclerosis, histologically confirmed glomerulonephritis, cystic kidney disease and the miscellaneous were 27.1% (n=3,323), 17.0% (n=768), 8.4% (n=62), 13.9% (n=67), and 19.7% (n=5,435), respectively. Kaplan-Meier survival analysis showed that diabetic nephropathy was worst survival rate following hypertensive sclerosis, cystic kidney disease and the miscellaneous, while histologically confirmed glomerulonephritis showed highest survival rate (log-rank p < 0.001). After adjusting for confounders, cox-proportional regression analysis revealed that 5-year mortality was associated with diabetic nephropathy compared hypertensive nephrosclerosis (HR, 1.62 CI, 1.17-2.24) while histologically confirmed glomerulonephritis was not significant. Conclusion The overall mortality was associated with primary renal disease in hemodialysis paitents. This result suggests that hemodialysis patients with diabetic nephropathy require further medical attention.