Every-Other-Day Valganciclovir Prophylaxis for Cytomegalovirus Prevention in Kidney Transplant Recipients: A Single-Center Experience

Background: Moderate-risk for Cytomegalovirus (CMV) infection includes patients with donor positive/recipient positive (D+/R+) or donor negative/ recipient positive antibody status (D-/R+). Guidelines recommend high-dose daily Valganciclovir (VGCV) as prophylaxis, which may be due to the paucity of data on the efficacy of every-other-day VGCV. Methods: Our experience of using every-other-day VGCV as a prophylactic strategy in moderate risk Kidney Transplant Recipients (KTR) has been described. We retrospectively reviewed 86 moderate-risk KTR in our institution between 2018 and 2020. CMV infection at 6 months post-transplant was the primary endpoint. Graft survival, biopsy-proven rejection, opportunistic infections, Haematological adverse events, and mortality were also evaluated. Results: CMV infection occurrence at 6 months was zero in our cohort. Incidence of leukopenia was 13%, BPAR-31%, OI-33%, and mortality being 3.5%. Conclusion: Every-Other-Day VGCV dosing can be an effective alternative in moderate risk KTR for CMV prevention.

Dietary Sodium Restriction in the Management of Chronic Kidney Disease: A Meta-Analysis of RCTs

Introduction: Non-pharmacological strategies such as lowering sodium intake aim to protect renal function and delay the initiation of renal replacement therapy. It might also be a cost-effective method to improve Chronic Kidney Disease (CKD) prognosis. We decided to perform a meta-analysis of Randomized Controlled Trials (RCTs) to evaluate the effects of low versus high sodium intake in adults with CKD. Methodology: We searched the online databases – PUBMED, Cochrane Kidney and Transplant Specialized Register, Cochrane Library and Google Scholar to 31st December 2020 for RCTs to be included in the study. Meta- Analysis was performed for the intervention groups for each arm against the control. Inverse variance methods were applied for analysis using random effects models due to the high heterogeneity among the studies. Results: Our search strategy yielded seven studies from six countries with 465 participants. The overall effect on restricted sodium intake favored reduction in systolic blood pressure with an overall mean difference of -6.14(95% CI: -9.52, -2.76) and reduction in diastolic blood pressure with a mean difference of -3.08 (95% CI: -4.62, -1.55). There was lowering of estimated Glomerular Filtration Rate (eGFR), however the same was not statistically significant. Conclusion: The study found that restricted salt intake could significantly reduce systolic and diastolic BP. Further, multi-center RCTs for longer durations across different stages of CKD could effectively assess the effects of restricted sodium intake on vital parameters. Such study designs could also help clinicians identify the optimal intake of dietary sodium to achieve better renal and cardio vascular outcomes.

Association of Kidney-Related Safety Events with Incident Chronic Kidney Disease in Veterans

Objective: The impact of Nonsteroidal Anti-Inflammatory Drugs (NSAID) and iodine-based contrast exposures on developing Chronic Kidney Disease (CKD) is controversial. We examined the association of these exposures with the development of CKD in a Veteran population. Methods: A retrospective case-control study of 154,448 veterans from the Veterans Affairs (VA) Corporate Data Warehouse (CDW) database between 2005 and 2014 was conducted to assess the association between incident stage 3 CKD with Acute Kidney Injury (AKI), NSAID use, iodine-based contrast exposures, and comorbid conditions. Stepwise logistic regression was used to determine multivariable adjusted Odds Ratios (OR). Results: The mean age was 59 (SD±13), and the median eGFR was 84 (IQR: 73, 96). AKI was associated with increased odds of CKD (inpatient: OR=3.76, 95% CI: 3.44, 4.11; outpatient: OR=4.73, 95% CI: 4.09, 5.46) and demonstrated escalated odds with >1 episode (inpatient: OR=5.72, 95% CI: 4.71, 6.95; outpatient: OR=8.36, 95% CI: 6.32, 11.06). Months of NSAID prescriptions was associated with CKD, with ORs at >0-6 months, >6-12 months, and >12 months of 1.27 (95% CI: 1.23, 1.32), 1.54 (95% CI: 1.46, 1.63), and 1.69 (95% CI: 1.62, 1.77) respectively. Iodine-based contrast exposure was associated with increased odds of CKD, with ORs for 1-2 Computed Tomography (CT) scans, ≥3CT scans, and left heart catheterization of 1.29 (95% CI: 1.24, 1.35), 1.29 (95% CI: 1.20, 1.28), and 1.38 (95% CI: 1.17, 1.63) respectively. Conclusion: AKI events, NSAID use, and iodine-based contrast exposures are associated with increased odds for developing stage 3 CKD in veterans.

Metastatic Pulmonary Calcification in a Hemodialysis Patient after Renal Transplantation

This is the case of a 64-year-old man, on renal replacement therapy since 2008, due to autosomal dominant polycystic kidney disease. The patient was on peritoneal dialysis from 2008 to 2016, when he underwent renal transplantation. Transplant duration was less than a month due to acute vascular rejection. Since then, he is on hemodialysis. A few months after transplantation, it was incidentally identified confluent bilateral opacities, more prominent on the left lung in a routine X-ray (Figure 1). The patient had made a chest radiography in 2015 without any changes at that time. The CT scan showed parenchymatous densification areas, partially calcified, in both lungs (Figure 2). The patient also developed secondary hyperparathyroidism refractory to medical therapy but refused surgery. Nevertheless, the lesions had a slow progression until the present time.

Role of Renin-Angiotensin System, Renal Nerve System, and Oxidative Stress in Chronic Stress-Induced Renal Expression of Aquaporin-1 in Rats

Aims: To investigate the renal aquaporin-1 (AQP1) expression under chronic stress (induced by foot shock) condition and possible mechanisms involved in rats. Methods: The chronic stress model was established in male Sprague Dawley (SD) rats by foot shock for two weeks. Rats were randomly divided into control group, chronic stress group, renal denervation group, renal denervation plus chronic stress group, captopril (an angiotensin I converting enzyme inhibitor, ACEI) plus chronic stress group and tempol (a superoxide dismutase mimetic) plus chronic stress group. Body weight, food intake, water intake, blood pressure and heart rate were monitored. Real-time PCR was used to detect the mRNA level of AQP1 in the renal tissue. Immunohistochemistry stain was used to observe the expression and location of AQP1 in rat kidneys. Results: Chronic stress reduced body weight gain and food intake, while it significantly increased systolic blood pressure and renal expressions of mRNA and protein of AQP1 (P<0.05) as compared with control group. Renal denervation and tempol treatments did not affect stress-induced decreases of body weight gain and food intake. Renal denervation, captopril and tempol treatments decreased systolic blood pressure. Compared with the chronic stress group, mRNA and protein expression of AQP1 was decreased (P<0.05) in renal denervation plus chronic stress group, captopril plus chronic stress group and tempol plus chronic stress group. Conclusion: Chronic stress induces increase of the AQP1 expression in kidney, which is regulated by renal nerve system, renin-angiotensin system and oxidative stress.

Matrix metalloproteinase 9 Contributes to Glomerulosclerosis by Causing Profibrotic Changes in Podocytes and Glomerular Endothelial Cells

Background: Glomerulosclerosis is characterized by progressive (myo) fibroblast accumulation and collagen deposition involving profibrotic changes of podocytes and endothelial cells. A profibrotic role of MMP-9 in interstitial fibrosis has been reported. Whether MMP-9 plays a role in glomerulosclerosis is not clear yet. Methods: Mouse glomerulosclerosis model [Adriamycin Nephropathy (AN) model] was induced by a single adriamycin injection (10.2mg/kg, with physiological saline for controls) through tail vein in MMP-9-/- and wild-type control mice of BALB/c background. All animals were sacrificed at 4 weeks after injection. Albuminuria (albumin to creatinine ratio) and calculated GFR were measured. Gomori Trichrome (GT) and Sirius Red (SR) staining were used for assessment of glomerular fibrosis. Profibrotic changes of podocytes or glomerular endothelial cells were examined by confocal microscopy using immunofluorescence staining (IF) of desmin or a-SMA with P-cadherin or VEcadherin. Results: Albuminuria was reduced while GFR was increased in MMP-9-/- AN mice compared with those of wild-type mice. Confocal microscopy showed a significant decrease in podocytes double-stained with P-cadherin and desmin, demonstrating that MMP9-/- AN mice were protected from profibrotic changes in podocytes and glomerular endothelial cells. Glomerulosclerosis was significantly reduced in MMP9-/- AN mice compared to that of WT, as demonstrated by GT and SR staining. Conclusions: MMP-9 contributes to glomerulosclerosis at least in part by causing profibrotic changes in podocytes and glomerular endothelial cells.

Quality of Care in Long-Term Hemodialysis Patients in Mexico

Introduction: The End Stage Renal Disease (ESRD) is one of the leading causes of mortality in Mexico. The quality of care these patients receive remains uncertain. Methods: This is a descriptive, single-center and cross-sectional cohort study. The KDOQI performance measures, hemoglobin level >11 g/dL, blood pressure <140/90 mmHg, serum albumin >4 g/dL and use of arteriovenous fistula of patients with ESRD on hemodialysis were analyzed in a period of a year. The association between mortality and the KDOQI objectives was evaluated with a logistic regression model. A linear regression model was also performed with the number of readmissions. Results: A total of 124 participants were included. Participants were categorized by the number of measures completed. Fourteen (11.3%) of the participants did not meet any of the goals, 51 (41.1%) met one, 43 (34.7%) met two, 11 (8.9%) met three, and 5 (4%) met the four clinical goals analyzed. A mortality of 11.2% was registered. In the logistic regression model, the number of goals met had an OR for mortality of 1.1 (95% CI 0.5-2.8). In the linear regression model, for the number of readmissions, a beta correlation with the number of KDOQI goals met was 0.246 (95% CI -0.872-1.365). Conclusion: The attainment of clinical goals and the mortality rate in our center is similar to that reported in the world literature. Our study did not find a significant association between compliance with clinical guidelines and mortality or the number of hospital admissions in CKD patients on hemodialysis.

Dysproteinemia-Associated Kidney Diseases: Clinicopathological Correlations

Introduction: Dysproteinemia-associated kidney diseases can have diverse clinical and histological presentation but not all patients with monoclonal gammopathy have Monoclonal Gammopathy of Renal Significance (MGRS) and some have other causes for kidney lesions. Therefore, kidney biopsy is essential to make this diagnosis. We made a retrospective study, which aimed to: 1. Identify dysproteinemiaassociated kidney lesions; 2. Establish clinicopathological correlations of patients with those lesions and 3. Identify kidney and patient survival predictors. Methods: A retrospective, observational chart review of kidney biopsies performed, between January 2015 and February 2020, in three Portuguese Hospitals, to a total of 39 patients, with kidney lesions associated with monoclonal gammopathy, was undertaken. Results: The three main dysproteinemic kidney diseases identified were cast nephropathy, AL amyloidosis and Monoclonal Immunoglobulin Deposition Disease (MIDD), with different features among them. Only three patients fulfilled the criteria to Monoclonal Gammopathy of Renal Significance (MGRS). In regard to treatment, we verified that most of our patients were treated with chemotherapy. Unfortunately, only four recovered, either partially or completely. The mean kidney survival since kidney biopsy was 29,23 months and the mean patient survival since diagnosis was 24,46 months. Some clinical and pathologic features correlated to lowerkidney survival: acute tubular necrosis, cast nephropathy, Thrombotic Microangiopathy (TMA), haemoglobin and estimated Glomerular Filtration Rate (eGFR). Previous Nephrology follow-up correlated with higher kidney survival. Only eGFR was associated with lowerpatient survival.