A genome-wide association study suggests correlations of common genetic variants with peritoneal solute transfer rates in patients with kidney failure receiving peritoneal dialysis.

Movement of solutes across the peritoneum allows for the use of peritoneal dialysis to treat kidney failure. However, there is a large inter-individual variability in the peritoneal solute transfer rate (PSTR). Here, we tested the hypothesis that common genetic variants are associated with variability in PSTR. Of the 3561 participants from 69 centers in six countries, 2850 with complete data were included in a genome-wide association study. PSTR was defined as the four-hour dialysate/plasma creatinine ratio from the first peritoneal equilibration test after starting PD. Heritability of PSTR was estimated using genomic-restricted maximum-likelihood analysis, and the association of PSTR with a genome-wide polygenic risk score was also tested. The mean four-hour dialysate/plasma creatinine ratio in participants was 0.70. In 2212 participants of European ancestry, no signal reached genome-wide significance but 23 single nucleotide variants at four loci demonstrated suggestive associations with PSTR. Meta-analysis of ancestry-stratified regressions in 2850 participants revealed five single-nucleotide variants at four loci with suggestive correlations with PSTR. Association across ancestry strata was consistent for rs28644184 at the KDM2B locus. The estimated heritability of PSTR was 19%, and a permuted model polygenic risk score was significantly associated with PSTR. Thus, this genome-wide association study of patients receiving peritoneal dialysis bolsters evidence for a genetic contribution to inter-individual variability in PSTR.

Obesity and Mortality in End-Stage Renal Disease. Is It Time to Reverse the "Reverse Epidemiology"-at Least in Peritoneal Dialysis?

With the rising incidence of chronic kidney disease, there has been a steady growth of the hemodialysis (HD) and peritoneal dialysis (PD) population. Prevalence of obesity has also been on the rise. It has been proposed by some that obesity helps with survival in HD and possibly in PD patients-a concept called "Reverse Epidemiology." Here, we attempt to explore this phenomenon in the HD and PD populations and see specifically if it is time to reverse this concept. A MEDLINE search was performed using search terms: obesity, body mass index, end-stage renal disease, HD, PD, renal dialysis, mortality, survival, and reverse epidemiology. Review of recent literature questions the benefit of obesity on survival in the dialysis population-more specifically in PD. Patients on PD with higher muscle mass seem to have the best survival. There should be more focus on malnutrition among such patients.

Estimated GFR Before and After Bariatric Surgery in CKD.

BACKGROUND: Several reviews have recently detailed the beneficial effects of weight loss surgery for kidney function. However, these studies have a number of limitations, including small sample size, few done in chronic kidney disease (CKD) stages 3 and 4, and many not including the main bariatric surgery procedures used in the United States today. STUDY DESIGN: This was an observational retrospective cohort study comparing propensity score-matched bariatric surgery patients and nonsurgery control patients who were referred for, but did not have, surgery. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy were also compared using propensity matching. SETTING & PARTICIPANTS: Patients (714 surgery patients; 714 controls) were from a large integrated health care system, a mean of 58±8 (SD) years old, and mostly women (77%) and non-Hispanic whites (56%) and had diabetes mellitus (66%) and/or hypertension (91%). PREDICTOR: Predictors at the time of surgery or referral to surgery were age, sex, race/ethnicity, weight, and presence of diabetes and/or hypertension. OUTCOMES: The primary outcome for this study was change in estimated glomerular filtration rate (eGFR) from serum creatinine level over a median 3-year follow-up period. MEASUREMENTS: Serum creatinine was used to calculate eGFR using the CKD-EPI (CKD Epidemiology Collaboration) creatinine equation. RESULTS: Surgery patients had 9.84 (95% CI, 8.05-11.62) mL/min/1.73m2 greater eGFRs than controls at a median 3 years' follow-up and RYGB patients had 6.60 (95% CI, 3.42-9.78) mL/min/1.73m2 greater eGFRs than sleeve gastrectomy patients during the same period. LIMITATIONS: This study is limited by its nonrandomized observational study design, estimation of GFR, and large changes in muscle mass, which may affect serum creatinine level independent of changes in kidney function. CONCLUSIONS: Bariatric surgery, especially the RYGB procedure, results in significant improvements for up to 3 years in eGFRs for patients with CKD stages 3 and 4.

The relationship between kidney function and body mass index before and after bariatric surgery in patients with chronic kidney disease.

BACKGROUND: Improvements in kidney function post-bariatric surgery may be related to weight loss-independent effects. OBJECTIVES: To characterize the dynamic relationship between body mass index (BMI) and estimated glomerular filtration rate (eGFR) before and after bariatric surgery in patients with chronic kidney disease (CKD). SETTING: Kaiser Permanente Southern California (KPSC) health system. METHODS: We conducted an observational, retrospective cohort study of patients with CKD stage 3 or higher who received bariatric surgery at the KPSC health system between 2007-2015. Bariatric surgery procedures included primary Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) procedures. Outcomes consisted of mean trajectory estimates and correlations of BMI and eGFR taken between 2 years before and 3 years after surgery. Multivariate functional mixed models were used to estimate how BMI and eGFR trajectories evolved jointly. RESULTS: A total of 619 RYGB and 474 SG patients were included in the final analytic sample. The measurements were available before surgery for a median time of 1.9 years for SG and 1.8 years for RYGB patients. Median follow-up times after surgery were 2.8 years for both SG and RYGB patients. The mean age at the time of surgery was 58 years; 77% of patients were women; 56% of patients were non-Hispanic White; the mean BMI was 44 kg/m2; 60% of patients had diabetes mellitus; and 84% of patients had hypertension. Compared to the presurgery eGFR declines, the postsurgery declines in eGFR were 57% slower (95% credible interval [CrI], 33%-81%) for RYGB patients and 55% slower (95% CrI, 25%-75%) for SG patients. The mean correlation between BMI and eGFR was negligible at all time points. CONCLUSION: Though bariatric surgery slowed declines in eGFR up to 3 years after surgery, changes in eGFR tracked poorly with changes in BMI. This study provides evidence that the kidney-related benefits of bariatric surgery may be at least partly independent of weight loss. Confirming this hypothesis could lead to mechanistic insights and new treatment options for CKD.

COVID-19 Pandemic and the Burden of Acute Kidney Injury: The Known and the Unknown.

None: The present pandemic of severe acute respiratory syndrome is caused by the coronavirus (2019-nCoV), commonly called COVID-19. Starting from China, it has spread worldwide, causing major morbidity and mortality. It primarily involves the pulmonary system, but other organ systems are not spared. Treatment is still elusive and evolving. The exact pathogenesis of renal damage from COVID-19 virus and the magnitude of renal failure in this infection are not very clear. PubMed was searched to identify published literature from 2019 to present using the following keywords: COVID-19, acute kidney injury, creatinine, blood urea nitrogen, chronic kidney disease, renal replacement therapy, and dialysis. Cited references were also used to further identify relevant articles and literature elsewhere on the web. This review looks at the burden and influence of the COVID-19 pandemic on the kidneys and on the implications it will have on public health planning.

Medullary Sponge Kidney: Current Perspectives.

Medullary Sponge Kidney (MSK) disease is a rare congenital malformation of the distal nephron where cystic dilatation is appreciable in the collecting ducts and renal papillae. Most cases of the malformation are thought to arise from a malfunction within neurotrophic factor and tyrosine kinase interactions. Presentation and prognosis are usually indolent; however, they include urinary tract infections (UTI), nephrolithiasis and nephrocalcinosis, distal renal tubular acidosis (dRTA) and hypocitraturia. With an insidious and asymptomatic onset, MSK is a difficult renal manifestation to both diagnose and treat. Difficulty diagnosing MSK today arises from clinical settings deviating from the usage of contrast methods when assessing the urogenital tract. Many healthcare standards for kidney disorders center diagnosis around imaging techniques rather than contrast methods. This ultimately leads to a decrease in the total number of confirmed cases of MSK. Though intra-venous urogram (IVU) remains as the current gold standard to diagnose MSK, other methods such as endoscopy and Multi-detector computed tomography (MDCT) are being put into place. Endoscopic examination and renal biopsy may allow definitive diagnosis; however, such invasive methods may be considered excessive. Moving forward, differential diagnoses for MSK can be made more precisely when patients present with other renal manifestations, especially in groups at risk. These groups include patients between the age of 20 and 30, patients with other renal malformations, high sodium diet patients, hyperparathyroid patients, and patients with family history of MSK. Basic treatment is aimed at controlling stone formation by stabilizing urinary pH. Treatment for patients, especially those prone to forming stones, includes the application of potassium citrate compounds, prophylactic water and diet control, surgical intervention or lithotripsy for removal of symptomatic kidney stones.

Acquired Perforating Dermatosis in a Patient on Peritoneal Dialysis: A Case Report and Review of the Literature.

Acquired perforating dermatosis (APD) is a debilitating and itchy skin disease. Its diagnosis is based on biopsy and the treatment is not very clear. It is not well established as to how wide spread it is in patients on peritoneal dialysis (PD) and its implications in this population have not been well studied. Here we present a case of APD that developed in a patient on PD. Its pathology and treatment options are reviewed. More studies are needed to assess the prevalence of APD in PD population.

Changes in metformin use in chronic kidney disease.

Metformin is one of the oldest and most widely prescribed antidiabetic medicines worldwide. It is the only such medicine that has shown a reduction of cardiovascular mortality in diabetes mellitus type 2. Since many diabetic patients have chronic kidney disease, its use is often curtailed by practitioners due to fear of lactic acidosis and the US Food and Drug Administration (FDA) warnings that, until recently, had been in place for decades. Current guidelines, though somewhat vague regarding dosages, clearly pave the way for spreading the use of metformin in patients with lower glomerular filtration rates. These guidelines also suggest moving away from just looking at serum creatinine to create a cut-off. Metformin's costs are lower, and in many underdeveloped countries this is the only medicine available for poor patients. More widespread use of metformin will further help with health care costs, as well as obesity. It will simplify the use of diabetes mellitus type 2 management with lower incidences of hypoglycemia. With all the mounting evidence, the FDA is finally requiring labeling changes regarding recommendations, to allow the use of metformin in patients with much reduced kidney function.

The triad of kidney, obesity, and bariatric surgery.

There is an epidemic of obesity in the USA. Obesity significantly increases the risk of developing chronic kidney disease. Multiple studies have shown overall health and mortalityrelated benefits of medical and surgical weight loss. Renal benefits of bariatric surgery include decrease in proteinuria and hyperfiltration. There have only been a few small studies in patients with abnormally low glomerular filtration rate (GFR) that have shown improvements in GFR postsurgery over a short term. Long-term and larger scale studies are needed to see if renal benefits of weight loss are sustained in post-bariatric surgery patients.

Propofol-related infusion syndrome: role of propofol in medical complications of sedated critical care patients.

BACKGROUND: Propofol is a popular anesthetic and sedative. Use of propofol has increased manifold in this country over the last decade, and it is most commonly used in intensive care settings. Its rapid action with short half-life, decreased cerebral oxygen consumption, and reduction of intracranial pressure are properties that have made it a favorite in the intensive care unit. Many of these patients are critically ill or injured and require prolonged sedation. Propofol has been associated with morbidity and mortality, and in such cases the question often arises regarding the role propofol plays in these complications. OBJECTIVE: To address the issue of propofol-related infusion syndrome and its management. METHOD: A hypothetical clinical vignette was created to give a classic presentation of propofol-related infusion syndrome. CONCLUSION: It is hoped that this short report will bring more awareness of this entity so that it will be considered in the differential diagnosis in sedated critical care patients.