Health Care Access, Socioeconomic Status, and Acute Kidney Injury Outcomes: A Prospective National Study.

Rationale & Objectives: Acute kidney injury (AKI) incidence and outcome in Kuwait are unknown. Moreover, non-Kuwaitis, who represent 66% of the population, have lower income, and their access to public health services is restricted compared with Kuwaitis who have free full access. Study Design: Observational prospective multicenter cohort study. Setting & Participants: Adult inpatients with AKI in 7 public hospitals from January 1 to December 31, 2021. Exposure: AKI identified using Kidney Disease: Improving Global Outcomes serum creatinine-based criteria. Outcomes: For hospitalized patients with AKI, the outcomes included 30-day outcomes of mortality, need for dialysis, kidney recovery rates, and differences in outcomes between Kuwaitis and non-Kuwaitis. Analytical Approach: A backward stepwise multiple logistic regression analysis was performed to assess possible independent risk factors for the outcomes. Results: We recruited 3,744 patients (mean age: 63 years; mean baseline estimated glomerular filtration rate [eGFR]: 66.7 mL/min; non-Kuwaitis: 42.3%), representing 3.2% of hospitalizations and 19.5% of intensive care unit (ICU) admissions. Non-Kuwaitis were significantly younger (57.6 vs 66.9 years), with higher baseline eGFR (73.1 vs. 62 mL/min), more frequent community acquired AKI (53.8% vs 46.7%), and AKI in summer (34.7% vs 26.9%). Dialysis was provided to 33.5% of patients, with a higher need for non-Kuwaitis (35.5% vs 32.1%). At 30 days, 34.4% of patients died, representing 24.8% of hospital mortality and 59.8% of ICU mortality. No differences in mortality or kidney recovery were noted between Kuwaitis and non-Kuwaitis. Low eGFR did not affect the mortality rate. Limitations: Observational nature and short follow-up period of 30 days only. Conclusions: AKI was associated with high dialysis need and mortality. Non-Kuwaitis accounted for less cases despite representing 66% of the population because they were younger with higher baseline eGFR and fewer comorbid conditions. Non-Kuwaitis had higher rates of community acquired AKI and AKI in summer and a higher need for dialysis but had similar mortality and complete kidney recovery rates.

Incidences of acute kidney injury (AKI), its management, and its outcomes are unknown in Kuwait. In addition, Kuwait has a large population of ethnically diverse expatriates who have lower income and do not enjoy the same level of access to public hospital services. We recruited hospitalized adults who have a diagnosis of AKI in several public hospitals in Kuwait. We analyzed characteristics, management, and outcomes data for more than 3,700 patients and found that AKI affects 3.2% of hospitalized patients. AKI leads to high dialysis utilization rates and causes high mortality rates. Although more Kuwaitis were affected by AKI, the mortality rates for Kuwaitis and non-Kuwaitis were similar. Non-Kuwaitis were younger with better baseline kidney function and fewer chronic diseases than Kuwaitis.

The genetic landscape of autosomal dominant polycystic kidney disease in Kuwait.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal monogenic disease, characterized by bilateral accumulation of renal fluid-filled cysts leading to progressive renal volume enlargement and gradual impairment of kidney function, often resulting in end-stage renal disease. Kuwait could provide valuable genetic insights about ADPKD, including intrafamilial phenotypic variation, given its large household size. This study aims to provide a comprehensive description of the pathogenic variants linked to ADPKD in the Kuwaiti population using multiple genetic analysis modalities and to describe and analyse the ADPKD phenotypic spectrum in terms of kidney function, kidney volume and renal survival. Methods: A total of 126 ADPKD patients from 11 multiplex families and 25 singletons were recruited into the study. A combination of targeted next-generation sequencing (tNGS), long-range polymerase chain reaction, Sanger sequencing and multiplex ligation-dependent probe amplification were utilized for genetic diagnosis. Clinical evaluation was conducted through renal function testing and ultrasonographic kidney volume analysis. Results: We identified 29 ADPKD pathogenic mutations from 36 families achieving an overall molecular genetic diagnostic rate of 112/126 (88.9%), including 29/36 (80.6%) in families. A total of 28/36 (77.8%) families had pathogenic mutations in PKD1, of which 17/28 (60.7%) were truncating, and 1/36 (2.8%) had a pathogenic variant in the IFT140 gene. A total of 20/29 (69%) of the identified ADPKD mutations were novel and described for the first time, including a TSC2-PKD1 contiguous syndrome. Clinical analysis indicated that genetically unresolved ADPKD cases had no apparent association between kidney volume and age. Conclusion: We describe for the first time the genetic landscape of ADPKD in Kuwait. The observed genetic heterogeneity underlining ADPKD along with the wide phenotypic spectrum reveal the level of complexity in disease pathophysiology. ADPKD genetic testing could improve the care of patients through improved disease prognostication, guided treatment and genetic counselling. However, to fulfil the potential of genetic testing, it is important to overcome the hurdle of genetically unresolved ADPKD cases.

Safety of Intravenous Iron in CKD Stage 3-5 Patients Not on Dialysis: A Retrospective Cohort Study.

Background: Iron deficiency is common in chronic kidney disease (CKD) patients not on dialysis (ND). Restoring depleted iron stores through intravenous (IV) route is faster and associated with less side effects. There is conflicting data regarding intravenous iron use and its impact on clinical outcomes in this population. Objective: This study aims at evaluating any negative clinical impact associated with IV iron use in CKD patients at stages (3-5) before dialysis. Design: Retrospective chart review. Setting and Population: Chart analysis of ND CKD 3-5 (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2) patients who received IV iron between January 2013 and January 2018 in 3 major hospitals in Kuwait. Methods: Outcomes analyzed were rates of all-cause hospitalizations, infection-related hospitalizations, mortality rates, and eGFR decline over 12 months after IV iron infusion in this population divided into 3 groups according to CKD stage. Results: A total of 738 patients were included in our analysis. Mean initial hemoglobin concentration was 111.5 ± 15.0 g/L in group 1 (CKD 3: eGFR 30-59 mL/min/1.73 m2), 103.6 ± 17.7 g/L in group 2 (CKD 4: eGFR 15-29 mL/min/1.73 m2), and 99.4 ± 14.5 g/L in group 3 (CKD 5: eGFR < 15 mL/min/1.73 m2 but not on dialysis). All-cause hospitalization and infection-related hospitalization were more common among group 3 subjects (adjusted odds ratio =2.12 [95% confidence interval, CI: 1.32-3.41] and 2.02 [95% CI: 1.15-3.55]), respectively. No deaths occurred during 12 months of follow-up. Limitations: Lack of control group, retrospective study. Conclusion: Intravenous iron use in CKD 3-5 ND is generally safe. Higher hospitalization rates in patients with eGFR <30 mL/min are possibly associated with lower baseline hemoglobin, lower baseline eGFR, and higher comorbidity burden, and not related to iron infusion.

Contexte: La carence en fer est fréquente chez les patients atteints d'insuffisance rénale chronique (IRC) qui ne sont pas sous dialyse (ND). Le rétablissement des réserves de fer par voie intraveineuse (IV) est plus rapide et associé à moins d'effets secondaires. Les données sur l'administration du fer par intraveineuse et son incidence sur les résultats cliniques dans cette population demeurent toutefois contradictoires. Objectif: Cette étude vise à évaluer tout effet clinique négatif associé à l'administration de fer IV chez les patients atteints d'IRC de stade 3 à 5 avant la dialyse. Type d'étude: Examen rétrospectif des dossiers médicaux. Cadre et population: Analyse des dossiers médicaux de patients atteints d'IRC de stade 3 à 5 (DFGe < 60 ml/min/1,73 m2) ND ayant reçu du fer IV entre janvier 2013 et janvier 2018 dans trois grands hôpitaux du Koweït. Méthodologie: Les taux d'hospitalisations toutes causes confondues et d'hospitalisations liées à une infection, le taux de mortalité et le déclin du DFGe ont été mesurés sur une période de 12 mois après la perfusion de fer. La population était divisée en trois groupes selon le stade de l'IRC. Résultats: L'analyse porte sur un total de 738 patients. La concentration initiale moyenne d'hémoglobine était de 111,5 ± 15,0 g/L dans le groupe IRC 3 (DFGe: 30-59 ml/min/1,73 m2), de 103,6 ± 17,7 g/L dans le groupe IRC 4 (DFGe: 15-29 ml/min/1,73 m2) et de 99,4 ± 14,5 g/L dans le groupe IRC 5 (DFGe < 15 ml/min/1,73 m2 sans dialyse). Les hospitalisations toutes causes confondues et les hospitalisations liées à une infection étaient plus fréquentes chez les sujets du groupe IRC 3 (rapport de cotes ajusté = 2,12 [IC à 95 %: 1,32-3,41] et 2,02 [IC 95 %: 1,15-3,55] respectivement). Aucun décès n'est survenu pendant les 12 mois de suivi. Limites: Absence de groupe témoin, étude rétrospective. Conclusion: L'administration de fer IV chez les patients atteints d'IRC de stade 3 à 5 ND est généralement sûre. Le taux d'hospitalisation plus élevé observé chez les patients présentant un DFGe < 30 ml/min est probablement attribuable à des mesures initiales plus faibles pour l'hémoglobine et le DFGe, de même qu'à une charge de comorbidité plus élevée, plutôt qu'à la perfusion de fer.

Interventional nephrology and vascular access practice: A perspective from South and Southeast Asia.

South and Southeast Asia is the most populated, heterogeneous part of the world. The Association of Vascular Access and InTerventionAl Renal physicians (AVATAR Foundation), India, gathered trends on epidemiology and Interventional Nephrology (IN) for this region. The countries were divided as upper-middle- and higher-income countries as Group-1 and lower and lower-middle-income countries as Group-2. Forty-three percent and 70% patients in the Group 1 and 2 countries had unplanned hemodialysis (HD) initiation. Among the incident HD patients, the dominant Vascular Access (VA) was non-tunneled central catheter (non-TCC) in 70% of Group 2 and tunneled central catheter (TCC) in 32.5% in Group 1 countries. Arterio-Venous Fistula (AVF) in the incident HD patients was observed in 24.5% and 35% of patients in Group-2 and Group-1, respectively. Eight percent and 68.7% of the prevalent HD patients in Group-2 and Group-1 received HD through an AVF respectively. Nephrologists performing any IN procedure were 90% and 60% in Group-2 and Group 1, respectively. The common procedures performed by nephrologists include renal biopsy (93.3%), peritoneal dialysis (PD) catheter insertion (80%), TCC (66.7%) and non-TCC (100%). Constraints for IN include lack of time (73.3%), lack of back-up (40%), lack of training (73.3%), economic issues (33.3%), medico-legal problems (46.6%), no incentive (20%), other interests (46.6%) and institution not supportive (26%). Routine VA surveillance is performed in 12.5% and 83.3% of Group-2 and Group-1, respectively. To conclude, non-TCC and TCC are the most common vascular access in incident HD patients in Group-2 and Group-1, respectively. Lack of training, back-up support and economic constraints were main constraints for IN growth in Group-2 countries.

Current Status and Future of End-Stage Kidney Disease in Gulf Cooperation Council Countries: Challenges and Opportunities.

There is a paucity of data on epidemiology along with an incomplete registry of end-stage kidney disease (ESKD), nephrologist workforce, and variability among the countries of Gulf Cooperation Council (GCC). The study is an observation, descriptive study which aimed to describe current ESKD burden, nephrologist density, and kidney care infrastructure in GCC. Responses to a questionnaire-based survey obtained from representatives of the Nephrology Societies of GCC countries were analyzed. The categorical variables were compared using Chi-square test. A P = 5% was considered as significant. The mean prevalence of ESKD per million populations (pmp) was 551, highest in Oman (1000/pmp), least in Qatar (347/pmp). Predominant etiology in GCC was diabetes mellitus (DM) and hypertension (HTN) (100%, each), followed by chronic glomerulonephritis (66.7%). A transplant registry was maintained by all GCC countries. Hemodialysis (HD) (67.2%) was the most opted modality of kidney replacement therapy (KRT), followed by kidney transplantation (22%) and peritoneal dialysis (9.6%); 1.0% of patients opted for conservative management. Unplanned initiation of HD was three times more common. The access distribution among incident and prevalent HD patients respectively was (i) nontunneled central catheter (nTCC) (58.7 ± 36.6 vs. 1.5 ± 1.5), (ii) tunneled central catheter (23.5 ± 29.9 vs. 33.6 ± 10.0), and (iii) arteriovenous fistula (17.3± 14.4 vs. 57.8 ± 11.86). Death and transplantation were the reasons for dropout from HD. GCC has adequate kidney care infrastructure. There are 1686 nephrologists [range: Bahrain 9, Kingdom of Saudi Arabia (KSA) 1279]. Qatar, KSA, and Kuwait provide training in kidney biopsy; all countries except Bahrain have formal training programs for nTCC placement. ESKD prevalence is high, DM, HTN; glome-rulonephritis (GN) is the most common causes. The need for KRT is expected to rise in GCC. HD is the predominant KRT modality with a high prevalence of dialysis catheters as vascular access.

Glomerulonephritis Histopathological Pattern Change.

BACKGROUND: Glomerulonephritides (GN) are relatively rare kidney diseases with substantial morbidity and mortality. They are often difficult to treat, sometimes with no cure, and can lead to chronic kidney disease (CKD) and end stage kidney disease (ESKD). Kidney biopsy is the diagnostic procedure of choice with variable indications from center to center. It helps in identifying the exact specific diagnosis, assessing the level of disease activity and severity, and hence aids in proper therapy and helps predicting prognosis. There is a global change of pattern of glomerular disease over the last five decades. METHODS: Retrospective analysis of all kidney biopsies (545 cases) that were done in patients over 12 year-old over last six years in four major hospitals in Kuwait. The indications for kidney biopsy were categorized into six clinical syndromes: nephrotic syndrome, sub-nephrotic proteinuria, nephrotic syndrome plus acute kidney injury (AKI), sub-nephrotic proteinuria plus AKI, isolated hematuria, and Unexplained renal impairment. We calculated the incidence of each type of kidney disease and indication of biopsy. RESULTS: most common indication of kidney biopsy was sub-nephrotic proteinuria associated with AKI in 179 cases (32.8%). Primary Glomerulonephritis was the main diagnosis that was reported in 356 cases (65.3%). Immunoglobulin A Nephropathy (IgAN) was the commonest lesion in primary glomerulonephritis in 85 (23.9%) cases. Secondary Glomerulonephritis was diagnosed in 134 cases (24.6%), 56 (41.8%) of them were reported as lupus nephritis cases. In young adults (below 18 years of age) there were 31 cases reviews, 35.5% were found to have minimal change disease (MCD). CONCLUSION: IgAN is the commonest glomerulonephritis in primary nephrotic syndromes in Kuwait over the past six years. Lupus nephritis is the leading secondary glomerulonephritis diagnosis.

PKD1 Duplicated regions limit clinical Utility of Whole Exome Sequencing for Genetic Diagnosis of Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited monogenic renal disease characterised by the accumulation of clusters of fluid-filled cysts in the kidneys and is caused by mutations in PKD1 or PKD2 genes. ADPKD genetic diagnosis is complicated by PKD1 pseudogenes located proximal to the original gene with a high degree of homology. The next generation sequencing (NGS) technology including whole exome sequencing (WES) and whole genome sequencing (WGS), is becoming more affordable and its use in the detection of ADPKD mutations for diagnostic and research purposes more widespread. However, how well does NGS technology compare with the Gold standard (Sanger sequencing) in the detection of ADPKD mutations? Is a question that remains to be answered. We have evaluated the efficacy of WES, WGS and targeted enrichment methodologies in detecting ADPKD mutations in the PKD1 and PKD2 genes in patients who were clinically evaluated by ultrasonography and renal function tests. Our results showed that WES detected PKD1 mutations in ADPKD patients with 50% sensitivity, as the reading depth and sequencing quality were low in the duplicated regions of PKD1 (exons 1-32) compared with those of WGS and target enrichment arrays. Our investigation highlights major limitations of WES in ADPKD genetic diagnosis. Enhancing reading depth, quality and sensitivity of WES in the PKD1 duplicated regions (exons 1-32) is crucial for its potential diagnostic or research applications.