Obesity is common in chronic kidney disease and associates with greater antihypertensive usage and proteinuria: evidence from a cross-sectional study in a tertiary nephrology centre.

Obesity is a treatable risk factor for chronic kidney disease progression. We audited the reporting of body-mass index in nephrology outpatient clinics to establish the characteristics of individuals with obesity in nephrology practice. Body-mass index, clinical information and biochemical measures were recorded for patients attending clinics between 3rd August, 2018 and 18th January, 2019. Inferential statistics and Pearson correlations were used to investigate relationships between body-mass index, type 2 diabetes, hypertension and proteinuria. Mean ± SD BMI was 28.6 ± 5.8 kg/m2 (n = 374). Overweight and obesity class 1 were more common in males (P = .02). Amongst n = 123 individuals with obesity and chronic kidney disease, mean ± SD age, n (%) female and median[IQR] eGFR were 64.1 ± 14.2 years, 52 (42.3%) and 29.0[20.5] mL/min/BSA, respectively. A positive correlation between increasing body-mass index and proteinuria was observed in such patients (r = 0.21, P = .03), which was stronger in males and those with CKD stages 4 and 5. Mean body-mass index was 2.3 kg/m2 higher in those treated with 4-5 versus 0-1 antihypertensives (P = .03). Amongst n = 59 patients with obesity, chronic kidney disease and type 2 diabetes, 2 (3.5%) and 0 (0%) were prescribed a GLP-1 receptor analogue and SGLT2-inhibitor, respectively. Our data provides a strong rationale not only for measuring body-mass index but also for acting on the information in nephrology practice, although prospective studies are required to guide treatment decisions in people with obesity and chronic kidney disease.

Neutrophil gelatinase-associated lipocalin (NGAL) is localised to the primary cilium in renal tubular epithelial cells - A novel source of urinary biomarkers of renal injury.

BACKGROUND: Primary cilia have been shown to play a central role in regulating epithelial cell differentiation during injury and repair. Growing evidence implicates structural and functional abnormalities of primary cilia in kidney epithelial cells in the onset and development of various kidney diseases including polycystic kidney disease (PKD). Neutrophil-gelatinase associated lipocalin (NGAL) has been identified as a reliable urinary biomarker of kidney injury. However, the mechanism by which this protein accumulates in patient urine samples has not been fully elucidated. METHODS: Human renal tubular epithelial cells (RPTECs) were exposed to previously characterized deciliating agents to assess mechanisms of primary cilium loss. Confocal immunofluorescent imaging was employed to visualise the effects on cilia. Western blot analysis was utilised to quantify the ciliary protein Arl13b in both RPTEC whole cell lysates and supernatants. Co-immunoprecipitation was used to demonstrate co-localisation of Arl13b and NGAL in urinary samples from a clinical Chronic Allograft Nephropathy (CAN) cohort. RESULTS: Immunofluorescent analysis revealed that NGAL was localised to the primary cilium in RPTECs, co-localizing with a ciliary specific protein, Arl13b. Deciliation experiments showed that loss of the cilia coincided with loss of NGAL from the cells. CONCLUSION: The accumulation of NGAL in supernatants in vitro and in the urine of CAN patients was concurrent with loss of Arl13b, a specific ciliary protein. The findings of this study propose that increased NGAL urinary concentrations are directly linked to deciliation of the renal epithelial cells as a result of injury.

Identification of Apolipoprotein AI as a serum biomarker of chronic kidney disease in liver transplant recipients, using proteomic techniques.

Chronic kidney disease (CKD) is a common complication post-orthotopic liver transplantation (OLT). Development of CKD is detected by monitoring serum urea and creatinine, however disease can occasionally be at an advanced stage before they become abnormal. Therefore, more accurate parameters are required. In order to identify novel biomarkers of CKD, serum was obtained from 47 OLT recipients with CKD (glomerular filtration rate <60 mL/min) and 23 with normal renal function (glomerular filtration rate >90 mL/min). Using the proteomic technique SELDI-TOF-MS, three protein biomarkers (55.6 kDa, 9.5 kDa and 11.4 kDa) were identified that, together, could stratify patients into cases or controls with a sensitivity and specificity of 93.6 and 91.3%, respectively. The area under the curve was 0.94. The primary splitter of the groups at 55.6 kDa was an alternative version of a molecule at 27.8 kDa, which was subsequently identified by 1-D SDS-PAGE and LC-ESI-MS/MS to be Apolipoprotein AI. Protein expression was shown to be reduced in CKD, by both ELISA (p = 0.057) and Western blot analysis (p = 0.003). Apolipoprotein AI is a novel, accurate marker of CKD post-OLT. It does require further validation in a large, more diverse patient population but could potentially improve detection of CKD.

Squamous cell carcinoma of the renal pelvis after curative retroperitoneal radiotherapy for seminoma.

We report the case of a 71-year-old male who presented with squamous cell carcinoma of the renal pelvis in a solitary functioning kidney, 34 years after orchidectomy and adjuvant retroperitoneal radiotherapy for stage II seminoma. This rare second malignancy occurred in the radiation treatment field. Second malignancies are an uncommon but serious sequela of radiotherapy, with potential for significant health problems in patients with complete remission of primary disease. To our knowledge, this is the first report of squamous cell carcinoma of the renal pelvis occurring after radiation treatment.

Chronic kidney disease post-liver transplantation.

BACKGROUND: Renal disease is a recognized complication of orthotopic liver transplantation (OLT). We aimed to determine the incidence of all stages of chronic kidney disease (CKD), as defined in the Kidney Disease Outcomes Quality Initiative Guidelines. We also wanted to determine the risk factors for development of CKD and its impact on patient survival. METHODS: All patients who underwent cadaveric OLT, from January 1993 until July 2004, were analysed. The glomerular filtration rate (GFR) was determined using the equation developed by the Modification of Diet in Renal Disease Study. Thirty potential risk factors were examined by univariate and multivariate ordinal logistic regression analysis. Kaplan-Meier survival analysis, the log-rank test and Cox regression analysis were performed to evaluate the survival data. RESULTS: A total of 230 patients were included (107 males and 123 females) with a mean age of 47.7 years (4.5-70.35). Mean follow-up was 5.57 years (0.53-16.5). The following was the 10 year cumulative incidence for each stage of CKD: 0/1, 9.61%; 2, 53.71%; 3, 56.77%; 4, 6.11%; 5, 2.62%. Female gender, age, pre-OLT proteinuria, lower GFR from 1 year and higher creatinine from 6 months were associated with progression of CKD. The use of tacrolimus had a favourable impact. A GFR <30 ml/min, the need for re-transplantation and fulminant hepatic failure were all associated with reduced patient survival. CONCLUSIONS: Moderate CKD was very prevalent. We identified the risk factors for progression of CKD and also that severe CKD was associated with reduced patient survival.

Amyloidosis in cystic fibrosis: a case series.

As the life expectancy of patients with cystic fibrosis increases, unusual complications including amyloidosis are increasingly recognised. We report three cases of amyloidosis including a unique case presenting with a hemorrhagic and thrombotic diatheisis. This complication of amyloidosis has never been reported in cystic fibrosis.