The Renal Histopathological Findings in Patients with Renal Allograft Dysfunction: A Retrospective Single Center Study.

INTRODUCTION: Despite many advances in the development of knowledge and application of new immunosuppressive medications over the past two decades, the improvement has only been seen in the short-term outcome of kidney transplantation while the long-term survival of kidney transplantation has not significantly improved. Allograft kidney biopsy may help to determine the causes of allograft dysfunction which may change the treatment strategy. METHODS: In this retrospective study, kidney transplant recipients who underwent kidney biopsy in Shariati hospital during the years 2004 to 2015, at least three months after the kidney transplantation, were included for evaluation. Chi-square, ANOVA, post-hoc LSD, and T-test were used for data analysis. RESULTS: A total number of 525 renal transplant biopsies were performed; 300 of them had complete medical records. The reported pathologies consisted of acute T-Cell mediated rejection (TCMR) (17%), interstitial fibrosis and tubular atrophy/chronic allograft nephropathy (IFTA/CAN) (15%), calcineurin inhibitor (CNI) nephrotoxicity (12.8%), borderline changes (10.3%), glomerulonephritis (GN) (8.9%), antibody mediated rejection (ABMR) (6.7%), transplant glomerulopathy (TG) (5.3%), normal (8.4%), and other pathologies (15.6%). C4d was positive in 19.9% of the biopsies. The pathology category had a significant correlation with allograft function (P < .001), but it had no significant relationship with age and gender of the recipient, donor and donor source (P > .05). Moreover, in about 50% of cases, treatment interventions were based on pathological results, which were effective in 77% of cases. The two-year graft and patient survival after kidney biopsy were 89% and 98%, respectively. CONCLUSION: Acute TCMR, IFTA/CAN, CNI nephrotoxicity were the most common causes of allograft dysfunction based on the transplanted kidney biopsy. In addition, pathologic reports were helpful for proper treatment.  DOI: 10.52547/ijkd.7256.

Percutaneous biopsy of kidney; comparison between prone position and sitting position.

INTRODUCTION: Percutaneous kidney biopsy has been established as a safe, reliable and minimally invasive method. This study aims to describe the author's experience with biopsy of the kidney and to compare the results in sitting position versus prone in terms of the complication rate. MATERIALS AND METHODS: Patients were divided into two groups: prone and sitting position according to the clinician's and patient's preference. Followed by kidney biopsy, a questionnaire was completed. Then, data and the mean number of glomeruli in each group were compared. RESULTS: Apart from sweat, presumably due to the prone position, no significant differences were found regarding the side effects including dizziness, seizure, nausea, and vomiting between the two groups. The number of glomeruli was not significantly different between two groups. CONCLUSION: In comparison with the prone position, kidney biopsy at sitting position is more comfortable at least for patients who seems couldn't tolerate prone position. We recommend sitting position for kidney biopsy owing to the low side effects rate of this diagnostic technique.

Association between low bone mass and the serum RANKL and OPG in patients with nephrolithiasis.

BACKGROUND: Nephrolithiasis is a risk factor for Osteopenia and osteoporosis. Receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) regulate bone remodeling and osteoclastogenesis. This study aimed to evaluate the relation between serum OPG, RANKL concentration, and bone mineral density (BMD) in patients with kidney stone disease. METHODS: Forty-four nephrolithiasis patients with either low bone mass or normal BMD (considered control group) were enrolled in this study. BMD was measured at lumbar spine (L1-L4) and femoral neck by dual-energy X-ray absorptiometry (DEXA). The serum OPG and RANKL were determined using the ELISA method. RESULTS: The median levels of serum OPG were significantly higher in nephrolithiasis patients with low bone mass compared to the nephrolithiasis patients with normal BMD (3.9 pmol/l versus 3.1 pmol/l; P = 0.03), respectively. Negative correlation was detected between bone densities of femoral neck and OPG in patients with nephrolithiasis (r = -.0344, P = 0.02). CONCLUSION: The present study showed that high serum fasting OPG levels may be indicative of femoral neck BMD in patients with nephrolithiasis.

Association of Brain-dead Donor's Urine Neutrophil Gelatinase-associated Lipocalin Levels With Kidney Allograft Function.

INTRODUCTION: Development of delayed graft function is more prevalent in patients receiving a kidney allograft from brain-dead than living donors. This study aimed to evaluate the association between urine neutrophil gelatinase-associated lipocalin (NGAL) levels in brain-dead donors and subsequent allograft function. MATERIALS AND METHODS: Urine NGAL concentration was measured in urine samples obtained from 24 brain-dead kidney allograft donors before organ retrieval. The 24 kidney recipients were followed for 6 months. The immunosuppressive therapy was similar for all of the recipients. Following transplantation, plasma creatinine was recorded daily during the recipient's stay in the hospital and then at 1, 3, and 6 months after transplantation. Delayed graft function was defined as the need for dialysis in the first 7 days after transplantation. RESULTS: The mean age of the donors was 28.7 ± 11.2 years and 70.8% were men. Their median urine NGAL level was 7.4 ng/ml (range, 2 ng/mL to 45 ng/mL). Urine NGAL levels were only associated with the need for cardiopulmonary resuscitation (P = .007). On the 1st day after transplantation, 16.7% of the recipients developed delayed graft function, which was declined to 12.5% on the 2nd day and to 8.3% during the 3rd day and the following days. No significant association was observed between the donor's urine NGAL levels and graft function (P = .86). CONCLUSIONS: Our results did not show any association between urine NGAL levels and outcome of allograft function obtained from brain-dead donors. Larger studies are required to confirm this finding.

Non-diabetic renal disease with or without diabetic nephropathy in type 2 diabetes: clinical predictors and outcome.

BACKGROUND: Renal involvement in type 2 diabetes is mostly due to diabetic nephropathy (DN), but a subset of diabetic patients could present with pure non-diabetic renal disease (NDRD) or NDRD superimposed on DN. We conducted a prospective cohort study to identify the underline renal pathology in type 2 diabetic patients with defined clinical criteria for renal biopsy. METHODS: A total of 46 patients (27 female, mean age of 48.9 ± 11.9 years) with type 2 diabetes mellitus (DM) and atypical features of DN with unexpected proteinuria, hematuria, and/or renal impairment were enrolled in this study. RESULTS: Of 46 patients with type 2 diabetes, 16 (34.8%) had DN, 20 (43.5%) had NDRD, and 10 (21.7%) had NDRD superimposed on DN. Membranous nephropathy (34%) was the most common NDRD. Patients with NDRD had a lower frequency of diabetic retinopathy (5%), shorter duration of diabetes, higher range of proteinuria, and better kidney survival. In multiple logistic regression analysis, only lack of diabetic retinopathy was independent predictor of NDRD. Positive and negative predictive value of diabetic retinopathy (DR) for diabetic nephropathy was 94 and 68%, respectively. CONCLUSION: Kidney biopsy is strongly recommended for patients with type 2 diabetes and atypical renal presentation for DN, particularly in the absence of DR. This approach could lead to diagnosis of NDRD with better renal survival.

Prospective study of BK virus infection and nephropathy during the first year after kidney transplantation.

INTRODUCTION: The aim of this study was to assess the prevalence and severity of BK virus infection, BK virus nephritis, and related risk factors among kidney transplant recipients. MATERIALS AND METHODS: BK viremia during the first year of kidney transplantation was assessed prospectively in 32 successive recipients. BK virus DNA was extracted and determined in all samples by real-time polymerase reaction assay for 1 year after kidney transplantation. RESULTS: The mean age of the patients was 33.3 ± 15.3 years. Sixteen patients (50%) received antithymocyte globulin for induction therapy. Living donor transplant consisted of 75% of the kidney donations. Maintenance immunosuppressive therapy included cyclosporine A in 27 patients (84.4%), plus tapering prednisolone and mycophenolate mofetil. BK viremia was detected in 8 patients (25%). The highest detected plasma viral load was less than 4000 copies per milliliter. BK virus was respectively positive in 5 (62.5%), 2 (25%), and 1 (12.5%) patients during the first 4, 8, and 12 months after transplantation. Biopsy-proven rejection and antirejection therapy by methylprednisolone pulses were 5 and 2.3 times more common in patients with BK virus infection (P = .01 and P = .01), respectively. CONCLUSIONS: Despite occurrence of BK virus infection in 25% of our patients, BK nephropathy did not develop in any of them. Routine screening of BK virus infection, particularly in centers with low prevalence of BK virus nephritis, may not be cost effective for predicting this disease.

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.

Adaptation and implementation of the "Kidney Disease: Improving Global Outcomes (KDIGO)" guidelines for evaluation and management of mineral and bone disorders in chronic kidney disease for practice in the Middle East countries.

This review presents the views of an expert group of nephrologists from the Middle East along with an international expert on adaptation and implementation of the 2009 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for evaluation and manage-ment of mineral and bone disorders in chronic kidney disease (CKD-MBD) for practice in the Middle East countries. The members of the panel examined the KDIGO guidelines and formulated recommendations that can be implemented practically for the management of CKD-MBD in the Middle East. There was a broad agreement on most of the recommendations made by the KDIGO work-group. However, the panelists commented on specific areas and amplified certain concepts that might help the nephrologists in the Middle East. The final document was reviewed by all participants as well as by members of the Middle East task force implementation group for KDIGO guidelines. Their comments were incorporated. The guideline statements are presented along with detailed rationale and relevant discussion as well as limitations of the evidence. The panel recognized the need to upgrade the suggestion of KDIGO related to lateral abdominal radiograph and echocardiogram in patients with CKD stages 3-5D into a stronger recommendation. The panel underlined the risk of hyper-phosphatemia to CKD-MBD and the importance of prompt initiation or modification of therapy according to rising trends in para-thyroid hormone level. They recommended the use of non-calcium-based phosphate binders as the first-line therapy in CKD patients with signs of vascular calcification. The panel agreed that all aspects of the KDIGO recommendations concerning bone biopsy, evaluation and treatment of bone disease after kidney trans-plantation should be implemented as such.

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.

PDpoietin in comparison with Eprex in treatment of anemic patients on hemodialysis.

INTRODUCTION: PDpoietin is a recombinant erythropoietin alfa that has been introduced by a manufacturer in Iran. We assessed the effectiveness and complications of PDpoietin in comparison with Eprex in anemic patients on hemodialysis. MATERIALS AND METHODS: This clinical trial was performed in a multicenter setting. Patients with a hemoglobin level less than 12 g/dL were assigned into 2 groups in order to receive either Eprex (Janssen Cilag) or PDpoietin (Pooyesh Darou) for 3 months. RESULTS: Forty-one and 34 patients completed the study in the PDpoietin and Eprex groups, respectively. The mean hemoglobin levels at baseline were not significantly different between the two groups of patients with PDpoietin and Eprex. In both groups, hemoglobin levels increased significantly, but there were no significant differences between the two groups at months 1, 2, and 3. At the end of the study, the mean hemoglobin levels reached 11.6 +/- 1.7 g/dL and 11.8 +/- 1.9 g/dL, respectively (P = .002; P = .01). The mean hemoglobin per cumulative of drug dose index (hemoglobin/[erythropoietin dose/1000 x injections per month]) was not significantly different between the two groups at different treatment stages, and it did not change significantly in each group during the course of the study. No serious complications were reported. CONCLUSIONS: Eprex and PDpoietin could equally increase the hemoglobin levels with no significant complication. Therefore, PD can be used for treatment of anemia in patients on dialysis, and the patients will have the advantages of its availability and low price.

Tacrolimus rescue therapy for corticosteroid-resistant and polyclonal antibody-resistant kidney allograft rejections.

INTRODUCTION: The conventional treatment of acute kidney allograft rejection consists of high-dose corticosteroids and polyclonal antibodies. We report our experience of tacrolimus rescue therapy in patients with acute rejections refractory to corticosteroids and polyclonal antibodies. MATERIALS AND METHODS: A total of 34 patients with a mean age of 42.3 years and clinical diagnosis of acute kidney allograft rejection underwent tacrolimus rescue therapy when treatment with corticosteroids and polyclonal antibodies failed. Kidney allograft biopsy results were available in 21 patients. All of the patients received tacrolimus, 0.1 mg twice daily, and in those who responded to the therapy after 4 to 6 months, tacrolimus was changed into cyclosporine. RESULTS: Pathologic examination of 21 biopsy specimens of the kidney allografts showed acute vascular rejection in 7 patients (33.3%), acute humoral rejection in 6 (28.6%), acute cellular rejection in 3 (14.3%), and accelerated acute rejection in 3 (14.3%). Twenty-six patients (76.5%) responded to rescue therapy with tacrolimus and discharged with a mean serum creatinine level of 1.4 mg/dL (range, 1.1 mg/dL to 1.7 mg/dL). Allograft nephrectomy was done in 8 patients (23.5%) because of no response to treatment of rejection, the pathology reports of which consisted of acute vascular rejection in 5 patients and extensive necrosis in 3. CONCLUSION: Tacrolimus therapy is able to salvage kidney allografts with acute refractory rejection. We recommend that tacrolimus be used as an alternative to the conventional drugs used for antirejection therapy. However, severe infectious complications as a result of overt immunosuppression must be considered.

Acute cellular rejection.

The incidence of acute rejection of the kidney allograft in the world has been around 15% during the period between 2001 and 2003. It is clinically defined as an elevation in the level of serum creatinine by more than 0.3 mg/dL and is diagnosed by kidney biopsy. On pathologic examination, the interstitium of the allograft is diffusely edematous and infiltrated by CD4 and CD8 lymphocytes. Tubulitis occurs when the lymphocytes and monocytes extend into the walls and lumina of the tubules. Presence of leukocytes determines infection or antibody-mediated rejection. Typically C4d staining is negative. Other causes of acute allograft dysfunction included prerenal factors, interstitial nephritis, infection, acute tubular necrosis, toxicity by drugs, and obstruction in the urinary tract. The primary diagnostic assessments include history, especially adherence to immunosuppressive therapy, physical examination, blood and urine laboratory tests, measurement of the serum levels of the drugs, and ultrasonography. Diagnosis of acute cellular rejection depends on biopsy, CD20 staining for refractory cases, negative C4d staining, presence of markers of activating lymphocyte, and proteomic study. Treatment of acute cellular rejection in kidney transplant recipients include pulse steroid for the first rejection episode. It can be repeated for recurrent or resistant rejection. Thymoglobulin and OKT3 are used as the second line of treatment if graft function is deteriorating. Changing the protocol from cyclosporine to tacrolimus or adding mycophenolate mofetil or sirolimus might be effective. Prognosis depends on number of rejection episodes, the use of potent drugs, time of rejection from transplantation, and response to treatment.