The Clinical Course and Prognostic Factors of COVID-19 in Patients with Chronic Kidney Disease, A Study in Six Centers.

INTRODUCTION: Coronavirus disease 19 (COVID-19), has recently emerged as a great health challenge. The novel corona virus may affect the kidneys mainly as acute kidney injury (AKI). Also, the outcome of COVID-19 may be different in patients with underlying kidney disease. The aim of this study was to compare the outcome of COVID-19 in patients with and without underlying kidney disease. METHODS: This was a retrospective study on 659 hospitalized COVID-19 patients in six centers of Iran. Patients were classified into kidney (chronic kidney disease (CKD), end-stage kidney disease (ESKD) or kidney transplantation) and non-kidney groups. The clinical conditions and laboratory data were extracted from the charts. Outcome was defined as death during hospitalization or within 30 days of discharge. RESULTS: Among 659 COVID-19 patients (mean age: 60.7 ± 16.4, 56% male), 208 were in the kidney group (86 ESKD, 35 kidney transplants, and 87 CKD patients). AKI occurred in 41.8%. Incidence of AKI was 34.7% in non-kidney, 74.7% in CKD, and 51.4% in kidney transplant patients (P < .001). Totally 178 patients (27%) died and mortality rate was significantly higher in CKD patients (50.6 vs. 23.4%, P < .001). AKI was associated with increased mortality rate (OR = 2.588, CI: 1.707 to 3.925). Initial glomerular filtration rate (GFR) < 44.2 mL/min and elevated lactate dehydrogenase (LDH) and C-reactive protein (CRP) had significant association with mortality. CONCLUSION: We showed a higher mortality rate in COVID-19 patients with AKI and CKD. Low initial GFR and elevated LDH and CRP were associated with high mortality in COVID-19 patients.

Impact of FGF23 level on calcium and phosphorus levels in post-renal transplantation.

Introduction: The level of fibroblast growth factor 23 (FGF23) may be considered as a prognostic factor for assessing renal function in regulating components of phosphate and vitamin D hemostasis. Objectives: The present study aimed to evaluate the prognostic value of FGF23 level to predict renal function after renal transplantation. Patients and Methods: Fifteen consecutive patients scheduled for renal transplantation. To assess renal function status, the MDRD formula and isotope scan were applied. The study endpoint was to assess the level of FGF23 and other factors involving calcium and phosphorus metabolism before and also 3 and 12 months after transplantation and also to determine role of FGF23 to predict postoperative renal function. Results: The mean level of FGF23 was 839.51±694.56 ρg/mL at baseline that reduced to 44.31±22.01 ρg/mL and 20.13±36.50 ρg/mL, 3 and 12 months after initial assessment. The levels of FGF23 was significantly lower at 3 and 12 months after baseline (P=0.01 and P=0.02, respectively) with no difference in FGF23 level between the time points of 3 and 12 months after transplantation. Baseline level of FGF23 was found to be higher in the patients with higher glomerular filtration rate (GFR), in older patients, in males, in those patients with diabetic nephropathy, in those with acceptable renal function than in patients who suffered transplant rejection. Conclusion: The level of postoperative FGF23 is an important marker for secretion of phosphorus from kidneys emphasizing the central role of FGF23 marker to regulate calcium and phosphorus metabolism after a successful renal transplantation.

Nephrotic Syndrome After Hematopoietic Stem Cell Transplant: Outcomes in Iran.

OBJECTIVES: Patients undergoing hematopoietic stem cell transplant have an elevated incidence of acute renal failure. However, the incidence of nephritic syndrome due to graft-versus-host disease is growing and is independently associated with chronic renal disease after this procedure. MATERIALS AND METHODS: We conducted a prospective study to examine the risk of chronic kidney disease in glomerulopathy patients following hematopoietic stem cell transplant with a follow-up of 10 years. RESULTS: In our follow-up of 14 patients (4 men and 10 women) who were diagnosed with nephrotic syndrome after hematopoietic stem cell transplant, in 10 patients (71%), biopsy showed membranous nephropathy associated with graft-versus-host disease. The remaining 4 patients had focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, or minimal change disease. All patients were treated with angiotensin receptor blockers, cyclosporine (Neoral), and prednisolone. During follow-up, 6 patients (43%) had heavy proteinuria and a rise in serum creatinine, and 1 patient (7%) needed hemodialysis. Eleven patients (79%) achieved complete remission of nephrotic syndrome, 5 (36%) remained hypertensive, and 3 (21%) did not respond to therapy.. CONCLUSIONS: The early diagnosis of nephrotic syndrome should be considered after hematopoietic stem cell transplant, and therapeutic outcome measures should be in place in advance. If this is done, we found that patients' response to treatment can be optimal, and their renal function and overall survival can improve.

PKD2 mutation in an Iranian autosomal dominant polycystic kidney disease family with misleading linkage analysis data.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disorder caused by mutation in 2 genes PKD1 and PKD2. Thus far, no mutation is identified in approximately 10% of ADPKD families, which can suggest further locus heterogeneity. Owing to the complexity of direct mutation detection, linkage analysis can initially identify the responsible gene in appropriate affected families. Here, we evaluated an Iranian ADPKD family apparently unlinked to both PKD1 and PKD2 genes. This is one of the pioneer studies in genetic analysis of ADPKD in Iranian population. METHODS: Linkage reanalysis was performed by regenotyping of flanking microsatellite markers in 8 individuals of the ADPKD family. Direct mutation analysis was performed by Sanger sequencing. RESULTS: Mutation analysis revealed a pathogenic mutation (c.1094+1G>A) in the PKD2 gene in the proband. Analyzing 2 healthy and 4 clinically affected members confirmed the correct segregation of the mutation within the family and also ruled out the disease in 1 suspected individual. Misinterpretation of the linkage data was due to the occurrence of 1 crossing over between the PKD2 intragenic and the nearest downstream marker (D4S2929). Homozygosity of upstream markers caused the recombination indistinguishable. CONCLUSION: Although analysis of additive informative polymorphic markers can overcome the misleading haplotype data, it is limited because of the lack of other highly polymorphic microsatellite markers closer to the gene. Direct mutation screening can identify the causative mutation in the apparently unlinked pedigree; moreover, it is the only approach to achieve the confirmed diagnosis in individuals with equivocal imaging results.

The effect of treatment with N-acetylcysteine on the serum levels of C-reactive protein and interleukin-6 in patients on hemodialysis.

Patients with end-stage renal disease (ESRD) are at an increased risk of cardiovascular disease due to many factors including inflammation and oxidative stress. N-acetylcysteine (NAC) is a thiol-containing anti-oxidant with anti-inflammatory properties. We aimed to assess the effect of three months treatment with oral NAC on the plasma levels of inflammatory mediators like interleukin-6 (IL-6) and C-reactive protein (hs-CRP) in patients on hemodialysis (HD). Twenty-four patients (nine males and 15 females) on maintenance HD were recruited in the study. Their mean age was 55.3 years. All the patients received oral NAC (600 mg twice a day) for a period of three months. The serum levels of biomedical parameters and IL-6 and hs-CRP were measured at baseline and three months after initiation of treatment. A significant decrease in serum levels of hs-CRP (22.4 vs. 5.2), IL-6 (8.1 vs. 3.6), parathyroid hormone (iPTH) (257.2 vs. 158.8), ferritin (632.0 vs. 515.1) and erythrocyte sedimentation rate (ESR) (54.2 vs. 38.3) was observed following NAC treatment. Female subjects presented with a significantly higher change in serum levels of hs-CRP compared with males (23 vs. 5.4). In three subjects who were less than 40 years old, the hs-CRP and IL-6 levels showed an increase following NAC treatment. Our study found that short-term oral NAC treatment might result in the reduction of IL-6 and hs-CRP in patients who are on regular HD. This suggests that patients with ESRD may benefit from the anti-inflammatory effects of NAC.

Association of overtime urine volume and ultrafiltration changes with patient survival in continuous ambulatory peritoneal dialysis patients.

BACKGROUND: Associations between patient survival and baseline urine volume (UV), ultrafiltration (UF) volume, and combined UV and UF were evaluated in Iranian continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: From 1995 to 2006, data on 1472 CAPD patients from 26 centers were collected. Demographic, clinical, and laboratory characteristics were analyzed using STATA software. Baseline UV was considered as an indicator of residual renal function and patients with an annual decrease of more than 250 cc/day were placed in decreasing UV group. The role of a new variable, net positive fluid removal, which defines as the combination of baseline UV and UF, was also evaluated. RESULTS: Patients with higher baseline UV were significantly more married and educated and candidate for CAPD based on positive selection criteria. In dichotomous categorization, mean of serum creatinine was lower and albumin was higher in patients with UV ≥ 1000 cc/day compared with UV < 250 cc/day. A significant correlation was found between baseline UV <250 cc/day and ≥1000 cc/day and patient survival. Patients with stable UV had better survival compared with patients with decreasing UV (p = 0.04). There was no correlation between UF and patient survival. Remarkable association with patient and technique survival and net positive fluid removal ≥2000 cc/day and <500 cc/day was observed. Multiple Cox regression analysis revealed significant correlation between net positive fluid removal ≥2000 cc/day and higher patient survival [p = 0.01, hazard ratio (HR) = 13.2], higher first albumin (albumin ≥ 3.5 mg/dL, p = 0.01, HR = 0.02), and lower negative selection (p = 0.0001, HR = 11.8). CONCLUSION: Loss of UV over time and lower net positive fluid removal increase mortality of PD patients.

Association of inflammatory biomarkers with metabolic syndrome in hemodialysis patients.

The relative importance of inflammatory markers in relation with metabolic syndrome (MeS) in hemodialysis (HD) patients is uncertain. This study investigated the association between MeS and high-sensitive C-reactive protein (hsCRP), hallmark of inflammation, and other inflammatory-related biomarkers. The study included 153 patients who were dialyzed at least for the last 3 months. The serum level of hsCRP was assessed by high-sensitive Enzyme-linked immunosorbent assay (ELISA). MeS was defined using the modified National Cholesterol Education Program Adult Treatment Panel III (ATP-III). Ninety-one HD patients (59.5%) were diagnosed as having MeS. Lower level of high-density lipoprotein-cholesterol (HDL-C) was the most prevalent MeS component (85.6%). The serum level of hsCRP in these patients was significantly higher than that in HD patients without MeS (2.3 ± 1.7 vs. 1.7 ± 1.6 mg/dL, p = 0.03). A significant linear increase in the hsCRP levels was found according to the number of MeS components (ß = 0.09, p = 0.022). The study concluded that increasing inflammatory biomarkers, especially hsCRP, is associated with MeS in HD patients.

Patient outcome in primary peritoneal dialysis patients versus those transferred from hemodialysis and transplantation.

BACKGROUND: According to the concept of integrated care, renal transplantation, peritoneal dialysis (PD), and hemodialysis (HD) should be considered three complementary methods of renal replacement therapy. This study tried to evaluate patient outcomes in three different groups of PD patients, namely primary PD patients, those transferred to PD with failing kidney transplant, and those transferred to PD from HD. METHOD: From January 1, 1995, to end of 2006 from 26 PD centers, 1,355 patients including demographic, clinical and laboratory data, which were monthly collected through questionnaires, were enrolled in the study. We compared patients' characteristics, factors affecting patient survival, and patient outcomes between primary PD patients (group 1, n = 1,067), patients transferred from transplantation (group 2, n = 43) and those transferred from HD (group 3, n = 245), which had been on HD for at least 3 months before switching to PD. RESULTS: There was no difference in the proportion of patients with diabetes in the three groups. Overall, 238 patients (17.5%) were transferred to HD but there was no significant difference in PD technique survival on between the three groups. Death occurred in 256 (24%), 3 (7%) and 65 (26.5%) subjects in groups 1, 2 and 3, respectively. Most patients (81.5%) in group 2 underwent re-transplantation. The Kaplan-Meier survival rates were not different between the three groups. In the Cox multiple regression model, age, presence of diabetes and serum albumin level significantly influenced patient survival. CONCLUSION: We concluded that PD could be considered safe for patients experiencing complications on HD, as well as for those with renal transplantation.

Low prevalence of BK virus nephropathy on nonprotocol renal biopsies in Iranian kidney transplant recipients: one center's experience and review of the literature.

OBJECTIVES: BK virus-associated nephropathy in renal transplant recipients has been increasing in frequency in recent years. This rise is probably because of widespread use of highly potent immunosuppressive regimens, and increased immunosuppression load leads to inability of the recipients to increase a successful antiviral immune response. The incidence of BK virus-associated nephropathy in different reports is between 1% and 10%, with an allograft loss in significant numbers of patients, especially when timely diagnosis and treatment is not restored. We report our experience on BK virus nephropathy in our institute. MATERIALS AND METHODS: All renal transplant biopsies performed at our center between 2001 and 2006 were immunohistochemically screened for the presence of PV-specific protein (SV40 Ag). The histologic diagnosis of BK virus-associated nephropathy was made upon the observation of morphologic changes in tubular epithelium and confirmation with immunohistochemical staining. We reviewed the clinical records of the subjects for demographic, clinical, and laboratory data. RESULTS: BK virus nephropathy was found in 0.93% of all investigated allograft biopsies (1/108) and in 1.04% of all recipients (1/96; mean age of recipients, 36.48±14.10 years; age range, 13-74 years); 54 of them were male (57%). Type of kidney transplant was living-unrelated donor 76 (79%), living-related donor 13 (14%), and deceased donor 7. Seventeen patients (18%) were transplanted for a second time. Immunosuppressive drugs in 87 of recipients (90%) were cyclosporine, mycophenolate mofetil, and prednisolone. Our patient who developed BK virus-associated nephropathy 9 months after transplant was a 37-year-old man on prednisone, cyclosporine, and azathioprine immunosuppresion. He lost his graft 4 months after diagnosis. CONCLUSIONS: Although BK virus nephropathy after renal transplant is uncommon, it is a serious complication causing loss of the allograft. It should be included in the clinical differential diagnosis of transplant dysfunction.

Renal involvement in patients with hepatitis C virus infection.

INTRODUCTION: Hepatitis C virus (HCV) infection is a hepatotropic virus causing a variety of extrahepatic immunological manifestations and is a risk factor of a variety of extrahepatic diseases, such as mixed cryoglobulinemia and membranoproliferative glomerulonephritis (MPGN), which is the most common glomerulonephritis. The aim of this study was to evaluate renal involvement in HCV-infected patients. MATERIALS AND METHODS: A total of 300 randomly-selected HCV antibody-positive outpatients at the HCV clinic of Shariati hospital were enrolled. Serum creatinine was measured and glomerular filtration rate was estimated accordingly. Urine proteinuria was measured in 24-hour urine samples. RESULTS: The patients were 249 men (83.2%) and 51 women (16.8%) with a mean age of 37.8 +/- 11.7 years (range, 18 to 70 years). Proteinuria was found in 12 HCV antibody-positive adults (4%), 1 of whom underwent biopsy. He was a 55- year-old man with a 4-month history of facial and lower extremities edema and 3-g proteinuria with a normal kidney function (glomerular filtration rate, 85 mL/min) and normocomplementemia. Kidney biopsy specimens showed MPGN. The frequency of low glomerular filtration rate was 0.7% (2 patients) in the HCV antibody-positive adults. There was no significant relationship between HCV seropositivity and low glomerular filtration rate. CONCLUSIONS: Our observations showed renal involvement in HCV antibody-positive patients. Among immune complex glomerular kidney diseases, MPGN without cryoglobulins is thought to be the most common in these patients.

Frequency, risk factors, and outcome of acute kidney injury following bone marrow transplantation at Dr Shariati Hospital in Tehran.

INTRODUCTION: Bone marrow transplantation (BMT) is a major modality for malignant and hematologic disorders. This procedure is associated with a high morbidity and mortality such as acute kidney injury (AKI). Many factors, such as therapeutic agents, irradiation, and graft versus host disease (GVHD) can cause AKI. Bone marrow transplantation conditioning therapy in Iran is based on drugs such as busulfan and cyclophosphamide and without irradiation therapy. The aim of this study was to evaluate the frequency, risk factors, and mortality of AKI among patients who underwent BMT. MATERIALS AND METHODS: Acute kidney injury was defined as doubling serum creatinine from baseline at any time during the first 180 days posttransplant. The risk of AKI in relation to non-total-body-irradiation-based conditioning regimen, type of graft (allograft and autograft), comorbidities, GVHD, drug toxicity, and veno-occlusive disease were examined in 375 patients with BMT. RESULTS: One hundred and forty-two patients (37.6%) developed AKI at a median of 18 days after transplant. A higher frequency of AKI was observed in patients who received cyclosporine A (40%), patients with allograft BMT (42.1%), and those who developed gastrointestinal GVHD (47.3%) .The remainder AKI cases were associated with amphotericin B, veno-occlusive disease, and hemolytic-uremic syndrome. CONCLUSIONS: The frequency of AKI in our patients with BMT remained high. Cyclosporine A and amphotericin B and the presence of GVHD and veno-occlusive disease increased the risk of AKI within the first 180 days after BMT.

Predictors of patient survival in continuous ambulatory peritoneal dialysis: 10-year experience in 2 major centers in Tehran.

INTRODUCTION: Many factors have been proposed to be associated with higher mortality in patients on continuous ambulatory peritoneal dialysis (CAPD). However, the relative importance of these factors may differ among patients with different characteristics. We evaluated survival of patients on CAPD and its influencing factors in Iran. MATERIALS AND METHODS: We enrolled 282 patients on CAPD between 1996 and 2006 at 2 major CAPD centers in Tehran. Patient survival was investigated during this period. Demographic characteristics, laboratory data, dialysis adequacy parameters, residual renal function, peritoneal transport characteristics, and nutritional status were assessed as potential predictors of the outcome. RESULTS: The mean duration of follow-up was 18.4 +/- 14.5 months. Sixty patients (21%) died during the studied period. In univariate analysis, age, body mass index, history and duration of hemodialysis before CAPD, diabetes mellitus, blood pressure, patient selection criteria, edema, peritonitis, renal residual function, urine volume, dialysis adequacy, and serum levels of cholesterol, triglyceride, intact parathyroid hormone, calcium, and albumin were predictors of patient survival. Multivariate analysis demonstrated that old age, diabetes mellitus, prior hemodialysis longer than 7 months, low serum albumin, calcium, trigelyceride, and parathyroid hormone levels independently predicted mortality, while the use of angiotensin-converting enzyme inhibitors was associated with a better survival. CONCLUSIONS: This study showed that older patients on CAPD and diabetics are at a higher risk of mortality. On the other hand, nutritional and metabolic factors are other predictors of mortality. Especial concern should be applied to good nutrition and treatment of comorbidities in these patients.