A Prospective Study of Eplerenone in the Treatment of Patients with Glomerulonephritis.

BACKGROUND: High aldosterone levels contribute to kidney disease progression, while spironolactone in combination with ACEi or ARBs can potentially reduce proteinuria and ameliorate kidney function deterioration. However, evidence on the impact of eplerenone in patients with glomerulonephritis is scarce. METHODS: In this prospective observational study, we assessed the effects of eplerenone in patients with biopsy-proven glomerulonephritis who were already treated with ACEi or ARBs. Patients received either eplerenone (25 mg daily) on top of ACEi or ARBs or standard treatment alone. Proteinuria (24 h total protein excretion), kidney function, blood pressure and serum K+ levels were assessed at 3, 6 and 12 months after the initiation of treatment. RESULTS: Sixty-six patients were included in the study. Eplerenone was administered in 30 patients, while 36 received only ACEi or ARB. Proteinuria decreased from 1768 to 1152 mg/24 h after 1 year of eplerenone treatment, while it remained stable in controls. Eplerenone showed significant impact on proteinuria in those with baseline proteinuria of >1000 mg/24 h. Patients who received eplerenone showed a reduction in systolic blood pressure, while eGFR and serum K+ levels remained stable. CONCLUSIONS: Addition of eplerenone has a beneficial effect on proteinuria in patients with glomerulonephritis and significant baseline proteinuria.

Normal saline versus balanced crystalloids in patients with prerenal acute kidney injury and pre-existing chronic kidney disease.

INTRODUCTION: Normal saline (N/S) and Ringer's-Lactate (L/R), are administered in everyday clinical practice. Despite that, N/S increases the risk of sodium overload and hyperchloremic metabolic acidosis. In contrast, L/R has lower sodium content, significantly less chloride and contains lactates. In this study we compare the efficacy of L/R versus N/S administration in patients with prerenal acute kidney injury (AKI) and pre-established chronic kidney disease (CKD). METHODS: In this prospective open-label study we included patients with prerenal AKI and previously known CKD stage III-V without need for dialysis. Patients with other forms of AKI, hypervolemia or hyperkalemia were excluded. Patients received either N/S or L/R intravenously at a dose of 20 ml/kg body-weight/day. We studied kidney function at discharge and at 30 days, duration of hospitalization, acid-base balance and the need for dialysis. RESULTS: We studied 38 patients and 20 were treated with N/S. Kidney function improvement during hospitalization and at 30 days after discharge, was similar between the two groups. Duration of hospitalization was also similar. Anion-gap improvement as expressed with Δanion-gap between discharge and admission day was higher in those patients that received L/R in comparison to those that received N/S and pH increase (ΔpH) was slightly higher in the L/R group. No patient required dialysis. CONCLUSIONS: Administration of L/R or N/S to patients with prerenal AKI and pre-established CKD had no significant difference in short or long term kidney function but L/R showed a better profile in acid-base balance improvement and Cl- overload in comparison to N/S.

Favorable effects of peritoneal dialysis in patients with refractory heart failure and overhydration.

BACKGROUND: Patients with refractory to optimal pharmacological treatment heart failure (HF) require frequent hospitalization. Peritoneal dialysis (PD) has been part of the management of such patients mainly for promoting ultrafiltration and management of overhydration independently of kidney function. The aim of this study was to evaluate the efficacy of PD, especially the use of icodextrin solutions and intermittent PD, in the hospitalization rate and cardiac functional status of patients with HF. METHODS: We conducted a retrospective study involving patients with New York Heart Association (NYHA) class IV HF and preserved renal function (estimated glomerular filtration rate (eGFR) > 25 ml/min), who were refractory to conservative treatment. Clinical data on weight loss, hospitalization rate before and after PD initiation, cardiac functional status, and technique complications during a 6-month observational period were analyzed. RESULTS: PD treatment was performed in 32 patients with a mean age of 63.8 ± 11.9 years and a follow-up of 20.78 ± 14.24 months. Hospitalizations were significantly reduced from 20.7 ± 13.7 to 7.7 ± 8.9 days/patients at 6 months. All patients showed improvement in NYHA class as well as in left ventricular ejection fraction. Overall, eGFR showed a significant decrease but only six patients reached end-stage renal disease. Complications included 18 cases of peritonitis. PD was well tolerated and no patient dropped out of the method. Survival rate reached 72% at 12 months but mortality rate was high with 23 patients dying at 16.65 ± 12.3 months after the initiation of treatment. Patients survival was not influenced by the type of PD modality or weight reduction achieved. CONCLUSIONS: PD showed to be a viable option for the treatment of patients with refractory HF leading to a better cardiac functional status and diminishing the number of hospital admissions.

Treatment of Mixed Dyslipidemia With Alirocumab in a Kidney Transplant Recipient: A Case Report.

Dyslipidemia is common in kidney transplant recipients owing to the disturbance of lipid metabolism caused by chronic kidney disease and the effect of immunosuppression on lipid metabolism. Patients receiving treatment with mammalian target of rapamycin inhibitors show more prominent lipid disorders, which are attributed mainly, but not only, to adipocyte lipid uptake disruption, lipolysis promotion and lipogenic gene expression enhancement. Dyslipidemias in kidney transplant recipients predispose these patients to an increased risk of developing cardiovascular disease; thus, current guidelines recommend treatment initiation with a statin, regardless of low-density lipoprotein cholesterol (LDL-C) concentration, with ezetimibe as a secondary option for patients who do not tolerate such therapy or for those with inadequate response. Treatment with pro-protein convertase subtilisin/kexin type 9 inhibitors such as alirocumab, although effectively reducing LDL-C in patients with chronic kidney disease, has not been evaluated in kidney transplant recipients. In this case report, we present a case of a female kidney transplant recipient who developed substantial dyslipidemia after everolimus initiation. This case was resistant to treatment with simvastatin/ezetimibe combination, and the patient subsequently received alirocumab. Our patient showed a mean reduction of 46.6% in LDL-C during an 18-month period after alirocumab initiation, which is comparable to the results of studies on patients with or without renal impairment. Furthermore, treatment with alirocumab proved to be well tolerated without adverse effects or interactions with the immunosuppression regimen.

Safety and Efficacy of Long-Term Administration of Dipeptidyl peptidase IV Inhibitors in Patients With New Onset Diabetes After Kidney Transplant.

OBJECTIVES: The appearance of new onset diabetes is common after kidney transplant. Treatment options are limited because of renal function-related contraindications, interactions with immunosuppressive drugs, and side effects. We investigated the long-term safety and efficacy of dipeptidyl peptidase IV inhibitors in renal transplant recipients with new onset diabetes. MATERIALS AND METHODS: We treated 12 patients with dipeptidyl peptidase IV inhibitors, and 5 patients received insulin monotherapy as initial treatment of new onset diabetes after kidney transplant. All patients were followed for 12 months after diagnosis. Glycosylated hemoglobin A1c, estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration equation), plasma immunosuppressive trough levels, serum lipids, blood pressure, and body weight were measured during outpatient visits. Effects of dipeptidyl peptidase IV inhibitors and insulin on the aforementioned parameters were measured to compare values at time of diagnosis versus mean values of the last 6 months of follow-up. RESULTS: Patients were treated with linagliptin (4 patients), sitagliptin (4 patients), vildagliptin (2 patients), and alogliptin (2 patients). Patients had a mean age of 59.4 ± 12 years and a mean glycosylated hemoglobin A1c of 6.6% at diagnosis, which was decreased to 6.1% (P = .03) at 1 year of follow-up. Renal function remained stable, and plasma tacrolimus levels did not appear to be affected. No significant differences were shown in serum total, low-density lipoprotein, and high-density lipoprotein cholesterol levels aftertreatment. Nevertheless,triglyceride levels were significantly reduced (from 214.4 to 174.9 mg/dL; P = .0039). A decrease in body weight was also observed. Finally, patients treated with dipeptidyl peptidase V inhibitors achieved better glycosylated hemoglobin A1c levels than those treated with insulin. CONCLUSIONS: Dipeptidyl peptidase IV inhibitors appear to be a safe, effective, and hypoglycemia-free option fortreatment of new onset diabetes in renaltransplant recipients and possibly provide better diabetes control than insulin therapy.

Case Report: Kidney Transplantation in a Patient With Acquired Agammaglobulinemia and SLE. Issues and Challenges.

Lupus nephritis in the context of Systemic Lupus Erythematosus (SLE) is characterized by an unpredicted course with remissions and flare-ups. Among others, it remains a significant cause of end-stage kidney disease (ESKD) in relatively young patients. Therapeutic regimens with newer immunosuppressive agents have been introduced in order to control SLE clinical manifestations more efficiently and limit organ damage induced by immune complex formation and sustained inflammation. Treatment is usually long-term, and the cumulative impact of immunosuppression is expressed through the increased frequency of infections and neoplasms. However, if the observed immunity dysregulation is secondary and pharmaceutically induced or there is a pre-existing, primary immunodeficiency that shares common pathogenetic pathways with SLE's autoimmunity is not always clear. Herein, we present the case of a 39-year-old woman, that reached ESKD due to lupus nephritis. After an upper respiratory cytomegalovirus (CMV) infection and concomitant CMV reactivations the investigation revealed significant immunodeficiency. Not long after the initiation of intravenous immunoglobulin (IVIG) administration, patient received a cadaveric kidney transplant. IVIG was continued along with standard immunosuppression so that both recurrent infections and allograft rejection are avoided. Patient is closely monitored, and her post-transplant course is remarkably satisfying so far. ESKD patients with immunodeficiency syndromes should not be excluded by definition from kidney transplantation.

The effect of vitamin K2 supplementation on vascular calcification in haemodialysis patients: a 1-year follow-up randomized trial.

PURPOSE: Vascular calcification (VC) is an independent risk factor for cardiovascular disease in hemodialysis patients while Matrix GLA protein (MGP) is one of the most potent inhibitors of VC and its activation is vitamin K dependent. The aim of this study is to investigate the role of oral vitamin K2 supplementation in the prevention of VC progression in haemodialysis patients. METHODS: We conducted a prospective randomized interventional study in patients on hemodialysis. Patients were randomly assigned to either receiving orally 200 µgr of vitamin K2 (vitamin K2/MK-7, Solgar) every day for 1 year or no treatment. Uncarboxylated MGP (uc-MGP) concentrations were quantified using ELISA at randomization, at 3 and at 12 months. Aortic calcification was evaluated using Agatston score after an abdominal computed tomography scan that was performed at the beginning and at 12 months of follow-up. RESULTS: There were 102 patients that were randomized. After 1 year of follow-up, 22 patients from the vitamin K2 group and 30 patients from the control group were included in the analysis. After 3 months of treatment, uc-MGP values remained unchanged in the vitK2 group but after 1 year were reduced by 47% (p = 0.005). Furthermore, uc-MGP at 1 year was increased by 12% in the control group. At 1 year, vitK2 group had significantly lower values of uc-MGP in comparison to controls (p = 0.03). Agatston score was increased significantly both in vitamin K2 and control group at 1 year with no difference between groups. CONCLUSIONS: Oral administration of vitamin K2 in patients on haemodialysis reduced serum uc-MGP levels but did not have an effect in the progression of aortic calcification.

Biomarkers in Progressive Chronic Kidney Disease. Still a Long Way to Go.

The traditional chronic kidney disease (CKD) biomarkers (eGFR based on serum creatinine, sex and age and albuminuria) cannot predict a patient's individual risk for developing progressive CKD. For this reason, it is necessary to identify novel CKD biomarkers that will be able to predict which patients are prone to develop progressive disease and discriminate between disease processes in different parts of the nephron (glomeruli or tubules). A good biomarker should change before or simultaneously with lesion development and its changes should correlate strongly with lesion development. Also, there should be a close relationship between severity of injury and amount of detectable biomarker and its levels should decrease with diminishing injury. Among the large number of molecules under investigation, we have reviewed the most promising ones: NGAL and KIM-1, MCP-1, MMP-9, clusterin, MMP-9, TIMP-1, Procollagen I alpha 1 and suPAR. All these, have been studied as biomarkers for prediction of CKD progression in cohorts of patients with chronic kidney disease of different stages and various aetiologies (proteinuric and non-proteinuric, glomerulonephritides, diabetic, hypertensive and polycystic kidney disease). There is evidence that these molecules could be useful as biomarkers for progressive chronic kidney disease, however, the available data are not enough to draw final conclusions. Further studies with large cohorts and long follow-up are required to identify appropriate biomarkers, that will be able to accurately and reliably define the risk for progressive chronic kidney disease.

Long-Term Use of Cinacalcet in Kidney Transplant Recipients With Hypercalcemic Secondary Hyperparathyroidism: A Single-Center Prospective Study.

OBJECTIVES: Persistent secondary hyperparathyroidism is common after successful kidney transplant, with concomitant hypercalcemia and hypophosphatemia potentially leading to reduced graft survival and increased cardiovascular risk. Cinacalcet, a calcimimetic agent that activates the calcium-sensing receptors in parathyroid glands, is a therapeutic option. In this study, we assessed the long-term treatment effects of cinacalcet for a period of up to 5 years in a cohort of kidney transplant recipients. MATERIALS AND METHODS: Forty-seven patients with secondary hyperparathyroidism (intact parathyroid hormone level > 70 pg/mL or 7.43 pmol/L) and hypercalcemia (corrected calcium > 10.4 mg/dL or 2.6 mmol/L) were considered eligible for treatment with cinacalcet and were included in the analysis. Data were recorded at initiation of treatment and every 6 months up to a maximum follow-up of 60 months. A control group of patients treated with placebo, conventional treatment, or surgical treatment was not available for this study. RESULTS: Mean follow-up time was 45 ± 16 months. Treatment with cinacalcet was initiated at a median of 25 months after renal transplant. Serum calcium decreased by 0.21 mmol/L (2.69 vs 2.48 mmol/L; 95% confidence interval, 0.08-0.345; P < .001) during the first 6 months, and this reduction was sustained during follow-up. Intact parathyroid hormone level decreased by 7.68 pmol/L (32.96 ± 36.4 vs 25.28 ± 19.5 pmol/L; 95% confidence interval, -6.42 to 21.75; P = not significant) at 6 months, whereas at the end of follow-up intact parathyroid hormone level decreased further by 20.07 pmol/L (32.96 ± 36.4 vs 12.89 ± 5.73 pmol/L; 95% confidence interval, 2.02-38.1; P < .01). Mean starting dose of cinacalcet was 33.5 ± 10 mg/day. According to the therapeutic response, cinacalcet dose increased steadily and reached 51.1 ± 33 mg/day at the end of the observation period. Mean serum phosphorus increased significantly, whereas estimated glomerular filtration rate remained virtually stable throughout follow-up. Adverse reactions were observed in 4 patients, comprising mild gastro-intestinal complaints. CONCLUSIONS: Long-term treatment with cinacalcet in kidney transplant recipients with secondary hyperparathyroidism is effective in controlling hypercalcemia and correcting hypophosphatemia, without affecting graft function while being well-tolerated.