Risk factors associated with chronic kidney disease progression: Long-term retrospective analysis from Qatar.

INTRODUCTION: The risk factors influencing the natural course of chronic kidney disease (CKD) are complex and heterogeneous. Recognizing the factors associated with CKD progression can enable the identification of high-risk patients for more intensive treatment. PATIENTS AND METHODS: A retrospective evaluation of CKD patients was performed under follow-up between January 1, 2001 and December 31, 2016 at a tertiary health care center. RESULTS: Among 5370 screened patients, 1020 patients with complete data were included in the analysis. The median follow-up period for the studied patients was 9.3 years. Based on the analysis, 120 (11.8%) patients had reached end-stage kidney disease "ESKD" or death. The study revealed that the risk factors associated with reaching ESKD and/or death using Kaplan-Meier survival curve and log rank test included higher hemoglobin A1c among diabetic patients, higher grade of proteinuria, and non use of renin-angiotensin system blockers. The patients with CKD progression constituted 77.2% of all CKD patients. The study findings indicated that older age, Arab ethnicity, smoking habit, diabetes mellitus and hypertension (presumed as original kidney diseases) are among the significant risk factors associated with a further decline of the estimated glomerular filtration rate (eGFR) and further CKD progression. CONCLUSION: This study summarized the demographic and clinical risk factors associated with CKD progression and patients' outcomes among a unique and heterogeneous population in the state of Qatar. Intensive treatment of modifiable risk factors could be of value in halting the progression of CKD. However, prospective studies are warranted to confirm our findings.

Prediabetes and older age increase the risk of post-transplantation diabetes mellitus: Qatar experience.

Post-transplantation diabetes mellitus (PTDM) is a major complication in kidney transplant recipients leading to reduced allograft and patient survival. Given the high prevalence of diabetes in Qatar, which is twice the global average, we were interested in determining the incidence of PTDM, identifying risk factors, and comparing clinical outcomes in kidney transplant recipients with and without diabetes. We retrospectively followed up 191 adult kidney allograft recipients transplanted between January 1, 2012, and December 31, 2016, for a median of 41 months. A total of 76 patients (40%) had pre-existing diabetes. A total of 39 patients developed PTDM during follow-up; they represent 34% of patients who did not have diabetes prior to transplantation. Two thirds of PTDM occurred within 3-6 months post-transplantation. Prediabetes before transplant [OR = 6.07 (1.24-29.74), P = .026] older recipient's age at the time of transplantation [OR = 1.10 (1.00-1.20), P = .039] and average fasting blood sugar during 3-6 months post-transplant [OR = 1.06 (1.01-1.11), P = .010] were independently associated with PTDM. Patient and kidney allograft survival rates exceeded 97% in all groups. The incidence of PTDM in kidney transplant recipients living in Qatar is high. Older age and prediabetes are independent risk factors for developing PTDM.

Atypical Anti-Glomerular Basement Membrane Disease With Diffuse Crescentic Membranoproliferative Glomerulonephritis: Case Report and Review of Literature.

Anti-glomerular basement membrane (anti-GBM) disease occurs in fewer than two cases per million population. Patients usually present with features of rapidly progressive glomerulonephritis (RPGN) with or without pulmonary involvement. Anti-GBM disease is classically diagnosed by both demonstrating GBM linear immunofluorescence staining on kidney biopsy and detecting anti-GBM antibodies in serum. More than 90% of patients with anti-GBM disease either become dialysis-dependent or die if left untreated. Here, we report a 37-year-old man who presented with bilateral lower limb edema, hypertension, acute kidney injury (creatinine of 212 µmol/L), microscopic hematuria, and nephrotic range proteinuria (15 g/day). His kidney biopsy showed diffuse crescentic membranoproliferative glomerulonephritis and bright linear staining of GBM by immunoglobulin G consistent with anti-GBM disease; however, serum anti-GBM antibodies were negative. The patient was diagnosed with atypical anti-GBM disease and treated aggressively with intravenous pulse steroids, plasmapheresis, oral cyclophosphamide, and oral prednisolone with significant improvement in kidney function and proteinuria. Atypical anti-GBM disease should be considered in patients presenting with RPGN, even in the absence of serum anti-GBM antibodies. Early diagnosis and aggressive treatment in such cases are warranted to prevent irreversible kidney damage as the course of the disease might not be as benign as previously thought.

Hyperosmolality-mediated peritoneal microvascular vasodilation is linked to aquaporin function.

Glucose-based peritoneal dialysis (PD) solutions dilate the parietal and visceral peritoneal microvasculature by endothelium-dependent mechanisms that primarily involve hyperosmolality. This PD-mediated dilation occurs by active intracellular glucose uptake and adenosine Al receptor activation, and by hyperosmolality-stimulated glibenclamide-sensitive potassium channels. Both pathways invoke NO as a second messenger for vasodilation. We hypothesized that during crystalloid-induced osmosis, the osmotic water flux through the transendothelial water-exclusive aquaporin 1 (AQP1) channels is the primary mechanism whereby the endothelium is being stimulated to instigate hyperosmolality-driven vasodilation. Four microvascular levels (diameters in the range 6 - 100 microm) were visualized by intravital videomicroscopy of the terminal ileum in anesthetized rats. Microvascular diameters and flow were measured after topical exposure to a 5% hypertonic mannitol or 2.5% glucose-based PD solution, at baseline and after brief tissue pre-treatment (with 0.1% glutaraldehyde for 10 seconds) or after combined tissue pre-treatment and pharmacologic blockade of AQP1 with HgCl2 (100 micromol/L). Vascular endothelial integrity was verified by the response to acetylcholine (10(-4) mol/L) and sodium nitroprusside (10(-4) mol/L). The hyperosmolar solutions both caused rapid and sustained vasodilation at all microvascular levels, which was not altered by tissue pre-treatment. Inhibition of AQP1 completely abolished the mannitol-induced vasodilation and markedly attenuated the PD fluid-mediated vasodilation. Neither glutaraldehyde pre-treatment nor HgCl2 affected tissue integrity or endothelial cell function. We conclude that the peritoneal microvascular vasodilation caused by hyperosmolar PD fluid is instigated by the osmotic water flux through AQP1. Clinical PD solutions have components other than hyperosmolality that can induce endothelium-dependent peritoneal microvascular vasodilation independent of the AQP1-mediated osmosis.

Molecular mechanisms of peritoneal dialysis-induced microvascular vasodilation.

Peritoneal dialysis (PD) solutions dilate microvessels by undefined mechanisms. This vasodilation directly affects ultrafiltration and solute exchange during a PD dwell and is thought to account for the variable mass transfer area coefficient for small solutes during a glucose-based hypertonic dwell. We hypothesized that PD-mediated vasodilation occurs by endothelium-dependent mechanisms that involve endothelium energy-dependent K+ channels (K(ATP)), adenosine A1 receptor activation, and NO release. We used intravital videomicroscopy to study 3 levels of microvessels (A1 inflow arterioles about 100 microm diameter to pre-capillary A3 arterioles 10 - 15 microm diameter) in the terminal ileum of anesthetized rats under control conditions in vivo in a tissue bath. Ileum was bathed with hypertonic mannitol or 2.5% glucose-based PD solution (Delflex: Fresenius Medical Care North America, Waltham, MA, U.S.A.) with or without topical application of individual or combined specific inhibitors of the endothelium-dependent dilation pathways.: NO (L-NMMA), prostaglandin I2 (mefenamic acid), endothelium hyperpolarizing factor (glibenclamide), and adenosine A1 receptor antagonist (DPCPX). The mannitol and PD solutions induced rapid and sustained peritoneal vasodilation whose magnitude depended on microvascular level and osmotic solute. Combined inhibition of endothelium-dependent dilation pathways completely abolished the mannitol-induced hyperosmolality-mediated dilation at all microvascular levels, but selectively eliminated the PD solution-mediated A3 dilation. The K(ATP) and adenosine receptor antagonists, individually or combined, remarkably attenuated dilation in the smaller pre-capillary arterioles; NO inhibition, alone or combined with K(ATP) and adenosine receptor antagonists, eliminated the PD solution-induced dilation. The cyclooxygenase pathway is not involved in PD-induced dilation. Solutions for PD dilate the visceral peritoneal microvasculature by endothelium-dependent mechanisms, primarily the NO pathway. Adenosine receptor-activated NO release and K(ATP) channel-mediated endothelium hyperpolarization significantly contribute to vasodilation in the smaller peritoneal pre-capillary arterioles.

Eradication of hepatitis C virus infection in kidney transplant recipients using direct-acting antiviral therapy: Qatar experience.

INTRODUCTION: Hepatitis C virus (HCV) infection has detrimental effects on patient and graft survival after kidney transplantation. In the pre-direct-acting antiviral (DAA) era, treatment of HCV infection was associated with low response rates, poor tolerance, and increased risk of allograft rejection. However, DAAs have revolutionized HCV treatment. The aims of this study were to determine the impact of DAA on the sustained virologic response (SVR), renal function, and calcineurin inhibitor (CNI) levels and assess the tolerability to treatment in kidney transplant recipients with HCV infection in Qatar. METHODS: This retrospective study included the medical records of all kidney transplant recipients with confirmed HCV infection before January 1, 2020. All data were obtained from the patients' electronic medical records; these included patient demographics; virologic responses to treatment; serum creatinine levels during treatment; urine protein to creatinine ratios and CNI levels before, during, and after treatment; and side effects related to DAA therapy. RESULTS: A total of 27 kidney transplant recipients with HCV were identified, 23 of whom received DAA therapy. The length of treatment ranged from 12 to 24 weeks, and 52% of patients had HCV genotype 1 infection. The median log10 HCV RNA was 6.6 copies per milliliter. None of the patients had liver cirrhosis, and all of them achieved SVR. There was no statistically significant difference in the glomerular filtration rate before, during, and after treatment. Most patients had stable CNI trough levels during treatment and did not require dose adjustment. CONCLUSIONS: HCV infection was successfully eradicated by DAA therapy in kidney transplant recipients, with a 100% SVR rate. Moreover, DAA therapy was well-tolerated, and kidney function remained stable without an increased risk of rejection. These results are expected to drive the eradication of hepatitis C from the entire country.

Kidney Transplant Recipients Infected With Coronavirus Disease 2019: Retrospective Qatar Experience.

BACKGROUND: This study aimed to evaluate the incidence of coronavirus disease 2019 (COVID-19) infection on kidney transplant, mortality, and risk factors associated with infection acquisition and severe illness in kidney transplant recipients with COVID-19. METHODS: Of 693 kidney transplant recipients who reported to our center, 249 were tested for COVID-19 by throat and nasal swab reverse transcription polymerase chain reaction. Of these, 43 recipients tested positive and 206 recipients tested negative. Among the 43 positive recipients, 9 were treated within an isolation facility, 25 were admitted to the hospital, and 9 were admitted to the intensive care unit (ICU). Risk factors associated with positive results and ICU admission were evaluated. RESULTS: COVID-19 was found in 6% of transplant recipients. Asian ethnicity (p = .003), history of hypertensive nephropathy (p = .01), AB blood group (P = .04), and higher tacrolimus trough levels (P = .007) were more frequent in the COVID-19 positive than in the COVID-19 negative group. ICU admission was more frequent in recipients presenting with fever, shortness of breath, and acute allograft dysfunction. Renal replacement therapy was required in 3 (7%) of 43 recipients, and mortality was reported in 1 (2.3%) recipient. Acute allograft dysfunction was an independent risk factor for severe COVID-19 (odds ratio, 93.7; 95% confidence interval, 2.37-3710.94; P = .02). CONCLUSIONS: Higher tacrolimus targets may be associated with COVID-19 development. Acute kidney injury during the COVID-19 course may be a sign of severe disease. Prognostication of COVID-19 severity in kidney transplant recipients is crucial for early recognition of critical illness and may ensure early intervention.

Restructuring nephrology services to combat COVID-19 pandemic: Report from a Middle Eastern country.

Coronavirus disease 2019 has spread across the world and has been classified as a pandemic. It has overwhelmed the healthcare systems. Specifically, it has overstretched the intensive care units and renal replacement therapy services in many countries. In this paper, we discuss the reconfiguration of nephrology services in the State of Qatar during the current pandemic. We highlight the key strategies that have been implemented to ensure that renal replacement therapy capacity is not constrained in either the intensive care or ambulatory setting. Some innovative approaches for the safe delivery of ambulatory care to dialysis and kidney transplant patients are also discussed.

Mutational analysis of AGXT gene in Libyan children with primary hyperoxaluria type 1 at Tripoli Children Hospital.

Primary hyperoxaluria type 1 (PH1) is an inborn error of glyoxylate metabolism. It results from genetic mutation of the AGXT gene. The study objective was to verify the clinical and epidemiological patterns of PH1 in Libyan children at Tripoli Children Hospital confirmed by AGXT gene mutation. A descriptive case series study of 53 children with PH1 diagnosed between 1994 and 2015 was carried out in the Nephrology Unit at Tripoli Children Hospital. Diagnosis of PH1 was based on the clinical presentation (renal stones or nephrocalcinosis), positive family history of PH1, and high 24 h urinary oxalate. Sampling for AGXT gene mutation was collected from April 2012 to December. 2015. Among the 53 children included, males composed of 62.3% of patients. Their age at presentation ranged between two months and 20 years with a mean age of 55.4 ± 48 months. The parents of 81.1% of these patients had positive consanguinity. Forty (75.5%) patients were from South West (mountain area), and 16 (40%) of them were from Yefrin. The most common mutation found in this study was c.731T>C (p.lle244thr) seen in 32 (71%) of children, and interestingly, among these patients, 87.1% were homozygous in gene typing, 86.2% had positive history of consanguinity, 71.4% were from South West (mountain area), 96.6% had family history of PH1, and 20% presented with impaired renal function. The patients with this mutation were younger at presentation than that with other genes, and it was more prevalent among boys (61.3%). Thus, the most common gene mutation found in Libyan children with PH1 was c.731T>C (p.lle244thr) and this is more likely due to the strong genetic pooling caused by the high consanguinity rate which requires an extensive genetic counseling.

Intervention using vitamin D for elevated urinary albumin in type 2 diabetes mellitus (IDEAL-2 Study): study protocol for a randomised controlled trial.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. T2DM is associated with serious macro- and microvascular complications. In particular, diabetic kidney disease (DKD), which begins with excessive urinary albumin excretion, has a significant impact on affected individuals and is costly to healthcare services. Inhibition of the renin-angiotensin-aldosterone system (RAAS) with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) significantly reduces albuminuria in diabetes, but this effect is not observed in all those treated. Active vitamin D analogues have been observed to be reno-protective through inhibition of RAAS in animal and human studies. Therefore, it can be hypothesised that an active vitamin D analogue will have an additional benefit to ACEI/ARB treatment for albuminuria reduction in DKD. METHODS: The planned study is an ongoing non-blinded randomised controlled parallel-group trial examining the impact, in individuals with T2DM, of the addition of bioactive vitamin D (calcitriol) to RAAS inhibition treatment using ACI or ARB on urinary albumin excretion over a period of 26 weeks. The primary outcome measure is the urinary albumin creatinine ratio. It is planned for the study to recruit 320 participants. Other outcome measures of interest include 24-h urine albumin (24 h UA) excretion, estimated glomerular filtration rate (eGFR), blood pressure and quality of life. Safety will be assessed throughout. DISCUSSION: If the addition of calcitriol to RAAS inhibition with ACEI or ARB safely results in a significant reduction in albuminuria, the study adds to the body of evidence supporting a role for vitamin D in reno-protection, will inform clinical practice and could result in significant reduction of healthcare costs associated with DKD. TRIAL REGISTRATION: ISRCTN, ISRCTN86739609 . Registered on 7 June 2017. ClinicalTrials.gov, NCT03216564 . Registered on 13 July 2017.

Standard continuous ambulatory peritoneal dialysis therapy provides similar initial T-Kt/V regardless of the patient's peritoneal membrane transporter category: Single-center experience.

Patients on continuous ambulatory peritoneal dialysis (CAPD) are routinely evaluated using the peritoneal equilibrium test (PET) to determine the best method for achieving target total dialysis clearance (T-Kt/V). In this study, we tested the hypothesis that standard CAPD prescription would achieve an initial T-Kt/V of more than 1.7 in all the patients regardless of their PET measurements. This is a retrospective study that included patients who started standard CAPD of four two-liter exchanges per day. The study included 118 patients; their mean age was 51.5 years with a standard deviation (SD) of 14.39 years. There were 83 males (70.3%) and 35 females (29.7%). PET and Kt/V were performed during the first four to six weeks of the study. The PET classified the patients into four categories: 24 (20.3%), high transporters; 65 (55.1%), high average; 28 (23.7%), low average; and one (0.8%), low transporter. Patients were then divided in two groups: Group 1 comprised of the high transporters while Group 2 included all the other patients. The T-Kt/V of the two groups was similar; in Group 1, it was 2.57 (± 1.17) and in Group 2 it was 2.50 (± 0.88) (P = 0.77). The T-Kt/V of patients with no residual renal function was also similar; in Group 1 and Group 2 it was 1.8 (± 0.29) and 1.97 (± 0.56), respectively (P = 0.45). All patients in our study who started on standard CAPD treatment had an adequate initial T-Kt/V. Thus, our data demonstrate that all patients with end-stage renal disease can safely begin standard CAPD without PET, which only needs to be performed if the patient encounters trouble in his/her T-Kt/V or fluid removal.

Peritoneal dialysis, an expanding mode of renal replacement therapy in Qatar.

Qatar is one of the gulf countries with a current estimated population of 1.4 million. Diabetes mellitus, hypertension and chronic kidney diseases are major emerging epidemics, with an incidence of end-stage kidney disease (ESKD) of 202 patients per million population per year. Peritoneal dialysis (PD) was initiated in Qatar in 1997 with a rapid expansion in the number of patients. The study included all patients performing PD in Qatar, during the period from 1 January 2003 to 31 December 2007. Retrospective analysis of data included the records of 241 patients in terms of their demography, treatment, complications, and survival. During the study period, PD patients formed 23% of all the dialysis population in Qatar, with a mean annual expansion rate of 12%. Diabetic nephropathy was the commonest cause of ESKD seen in 43% of PD patients. All age groups were included in our program, with a mean age of 53 ± 13 years. Males represented 74%. Continuous ambulatory peritoneal dialysis remained the initial mode of PD, with significant numbers being changed to automated PD over the years. The 1- and 5-year survival rates were 91% and 26%, respectively, with cardiac causes being responsible for 86% of mortality. The rate of peritonitis was 0.24 ± 0.1 episodes per patient years, and technique survival at 1 and 5 year was 84% and 32%, respectively. We conclude that the components of the PD program in Qatar are comparable to that in other countries with a good outcome.

Microbial spectrum and outcome of peritoneal dialysis related peritonitis in Qatar.

Peritoneal dialysis therapy rapidly expanded in Qatar during the last decade. Peritoneal dialysis related peritonitis remains the leading cause of morbidity and technique failure. The objective of this study was to determine the incidence of peritoneal dialysis related peritonitis in Qatar, during a five year study period. The records of all patients on maintenance peritoneal dialysis from January 1, 2003 to December 31, 2007 were reviewed. Episodes of peritonitis, microbial profile, clinical course and outcome were analyzed. A total of 241 patients were included, males represented 74%, the mean age was 53 + or - 13 years, and 48% of patients were diabetics. During the study period 118 episode of peritonitis were observed, with a mean incidence of 0.24 + or - 0.1 episodes per patient year. Gram-positive organisms were isolated in 40% of episodes, with Staphylococcus epidermidis and Staphylococcus hemolyticus being the commonest organisms, isolated in 21% and 9% of infections, respectively. Escherichia coli was the commonest Gram-negative organism and was isolated in 9% of peritonitis episodes, whereas culture-negative peritonitis represented 28% of all diagnosed infections. Seventy nine percent of peritonitis episodes completely resolved with the use of intraperitoneal antimicrobial therapy. Peritoneal dialysis catheters were removed in 19% of episodes. Peritonitis related mortality rate was 3%, and it was due to Candida spp. and Pseudomonas aeruginosa. Despite its low incidence, peritonitis remained the leading cause of patient dropout. Prompt diagnosis and prudent management as well as psychological support to the patients remained essential to reduce the incidence of technique failure following peritonitis episodes.

Demographic data and hemodialysis population dynamics in Qatar: A five year survey.

Hemodialysis was initiated in Qatar in 1981, since then the hemodialysis population has been expanding rapidly. This report describes the demographics and outcome of our hemodialysis patients during a five years study period. Data of all the patients on regular hemodialysis from January 1 st , 2002 to December 31 st , 2006 were included in this study was collected from the medical records and entered into an especially designed questionnaire. The prevalence of end stage kidney disease in Qatar is 624 patients per million populations with an incidence of 202 patients per million populations per year. Currently, 278 patients are on hemodialysis, 65% of them are Qatari, males represent 51%, whereas 44.6% are between 65-74 years of age. Diabetic nephropathy is the commonest cause of end stage kidney disease (48%), followed by primary glomerulonephritis and hypertensive glomerulopathy. Arteriovenous fistula was the vascular access in 57% of patients. The incidence of Hepatitis B, C and Human immunodeficiency virus had been stable throughhout the study period though our hemodialysis population had increased by 1.5 fold. The first and five years survival rates of our patients were 84 and 53% respectively. Qatar has one of the highest rates of dialysis patients with a good long-term survival report. Peritoneal dialysis remained to be the key solution for the rapidly expanding patients' pool. Maintenance of national registry of dialysis patients and improving our organ transplant program is an essential goal.