Serkan Akturk

Pregnancy After Kidney Transplantation: Outcomes, Tacrolimus Doses, and Trough Levels.

Although pregnancy after kidney transplantation has been considered as high risk for maternal and fetal complications, it can be successful in properly selected patients. It is well known that pregnancy can induce changes in the plasma concentrations of some drugs; however, there has been very limited information about tacrolimus pharmacokinetics during pregnancy. In this study, we evaluated the tacrolimus doses, blood levels, and the outcomes of pregnancies in kidney allograft recipients. From 2004 to 2014, we found 16 pregnancies in 12 kidney allograft recipients at our center. We reviewed the files and data reports including fetal outcomes, graft function, complications, tacrolimus trough levels, and doses. We analyzed the tacrolimus trough levels and doses before pregnancy, during pregnancy (monthly), and in the postpartum period. Throughout the pregnancy, we aimed to achieve tacrolimus trough levels between 4 and 7 ng/mL. All patients were on triple immunosuppression, including tacrolimus, azathioprine, and prednisolone. In total, 11 of 16 (68.7%) pregnancies were successful, with a mean weight gain of 12.5 ± 1.66 kg. One patient developed gestational diabetes mellitus and 2 had preeclampsia. Although 5 of 11 babies were found to have low birth weight, 4 of these were premature. Two patients lost their grafts, 1 due to acute rejection and the second due to progression of chronic allograft dysfunction. We have shown that tacrolimus doses need to be significantly increased to keep appropriate trough levels during pregnancy (the doses: before, 3.20 ± 0.9 mg/day; first trimester, 5.03 ± 1.5; second trimester, 6.50 ± 1.8; third trimester, 7.30 ± 2.3; post-partum, 3.5 ± 0.9). In conclusion, the dose of tacrolimus needs to be increased to provide safe and stable tacrolimus trough levels during pregnancy. Although pregnancy can be successful in most cases, it should be kept in mind that there is an increased risk of maternal and fetal complications, including allograft loss, low birth weight, spontaneous abortus, and preeclampsia.

Urgency Priority in Kidney Transplantation: Experience in Turkey

BACKGROUND In Turkey, according to the directions of National Organ and Tissue Transplant Coordination System, a system has been established since 2008 of urgency priority for kidney transplantation in cases with imminent lack of access for either hemodialysis or peritoneal dialysis. In this study, we compared patient and graft outcomes between patients on the national waiting list having urgency priority for kidney transplantation (UKT) and those having the other kidney from the same deceased donor (control group). METHODS We examined retrospective data of patients, who underwent transplantation under urgency priority allocation in Turkey from 2010 to 2014 and compared that group with other patients receiving kidney transplants from the same deceased donors (control group). Then we compared these patients for early and long-term patient and graft outcomes. RESULTS Forty-seven patients had UKT, and 40 patients received transplants from the same deceased donors. Mean follow-up of patients after transplantation was 18 ± 12 months. Eight patients with UKT and 4 patients in the control group lost their grafts. At follow-up, 7 patients died in the UKT group, and 4 patients died in the control group. Patient survival in the UKT group was 90% at 1 year and 83% at 2 years, and in the control group was 93% at 1 year and 84% at 2 years (P = .384). Graft survival was 87% at 1 year and 81% at 2 years in UKT, and 91% at both 1 and 2 years in the control group (P = .260). CONCLUSIONS Although patients with UKT showed lower graft and patient survivals than the control group, the difference was statistically nonsignificant. UKT can be an obligatory treatment model for patients with lack of vascular or peritoneal access for dialysis.

Colchicine-induced rhabdomyolysis following a concomitant use of clarithromycin in a haemodialysis patient with familial Mediterranean fever

Sir, Renal amyloidosis secondary to familial Mediterranean fever (FMF) is one of the common causes of nephrotic syndrome and chronic kidney disease in Turkey [1]. Colchicine is a microtubule-depolymerizing drug widely used for the treatment of gout which may prevent the development of secondary amyloidosis. In end-stage renal disease (ESRD), although the dose of colchicine is suggested to be reduced, there is limited information on efficacy and safety [2]. Inappropriately high doses or co-prescription of CYP3A4 or P-glycoprotein inhibitors have been reported to cause serious adverse effects, including death [3–7]. Herein, we present a case of colchicine-induced rhabdomyolysis after using clarithromycin, a macrolide antibiotic and a potent inhibitor of CYP3A4 and P-glycoprotein ABCB1. A 40-year old male patient on maintenance haemodialysis was admitted with recently developed fatigue, anorexia, headache, dizziness, diffuse myalgia and gastrointestinal symptoms including epigastric pain, diarrhoea and bloating. He presented with FMF in childhood (with frequent attacks of fever and abdominal pain with arthritis) and had developed secondary amyloidosis 10 years previously and ESRD 6 months previously. His long-term medication was colchicine 0.5 mg twice daily, doxazosin 4 mg once daily and 40 mg furosemide on non-dialysis days and sevelamer 1600 mg three times a day. A further history revealed that the patient had recently been diagnosed with acute sinusitis and was prescribed clarithromycin 500 mg twice daily in another hospital a week beofore. On his initial examination the patients blood pressure was 100/60 mmHg, he was in a euvolaemic state and had no significant finding except diffuse tenderness, but there was no rebound on abdominal palpation. In his biochemistry, his creatine kinase (CK)(5732 U/L- 9035 U/L) and transaminase levels (ALT:110 U/L, AST:309 U/L) were elevated and raised upon follow-up. Due to high CK and transaminases, colchicine-induced rhabdomyolysis was diagnosed and colchicine discontinued. The patients pain subsided 3 days after discontinuation of colchicine. An EMG was performed because of high levels of CK to exclude the diseases causing myopathie. During outpatient follow-up, the patients transaminases and CK returned to normal levels and his EMG was normal. After complete recovery, the patient started colchicine 0.5 mg/day again without recurrence of symptoms.

Kidney biopsy in AA amyloidosis: impact of histopathology on prognosis

Abstract In AA amyloidosis, while kidney biopsy is widely considered for diagnosis by clinicians, there is no evidence that the detailed investigation of renal histopathology can be utilized for the prognosis and clinical outcomes. In this study, we aimed to obtain whether histopathologic findings in kidney biopsy of AA amyloidosis might have prognostic and clinical value. This is a retrospective cohort study that included 38 patients who were diagnosed with AA amyloidosis by kidney biopsy between 2005 and 2013.The kidney biopsy specimens of patients were evaluated and graded for several characteristics of histopathological lesions and their relationship with renal outcomes. Segmental amyloid deposition in the kidney biopsy was seen in 29%, global amyloid deposition in 71, diffuse involvement of glomeruli in 84.2%, focal involvement in 7%, glomerular enlargement in 53%, tubular atrophy in 75% and interstitial fibrosis in 78% of patients. Histopathologically, glomerular enlargement, interstitial fibrosis, tubular atrophy, interstitial inflammation and global amyloid deposition were significantly associated with lower estimated glomerular filtration rate (eGFR) (p = .02, p < .001, p = .001, p = .009, p = .002, respectively) in univariate analysis. In multivariate analysis, tubular atrophy was the only predictor of eGFR (p = .019 B = −20.573). In the follow-up at an average of 27 months, 18 patients developed end-stage renal disease (ESRD). Among them, global amyloid deposition was the only risk factor for the development of ESRD (p = .01, OR = 18.750, %95 CI= 2.021–173.942). This is the first study showing that the histopathological findings in kidney biopsy of AA amyloidosis might have a prognostic and clinical value for renal outcomes.

Profile of renal AA amyloidosis in older and younger individuals: a single-centre experience

Abstract Objective: In epidemiological studies of amyloid A (AA) amyloidosis from Turkey, the most frequently cause was familial Mediterranean fever (FMF) and it occurs generally in young age population. However, there are no sufficient data regarding aetiology, clinical presentation and prognosis of renal AA amyloidosis in advanced age patients. In this study, we aimed to investigate demographic, clinical presentation, aetiology and outcomes of adults aged 60 years or older patients with biopsy-proven renal AA amyloidosis. Methods: This is a retrospective study involving 53 patients who were diagnosed with AA amyloidosis by kidney biopsy from 2006 to 2016. In all patients, kidney biopsies were performed due to asymptomatic proteinuria, nephrotic syndrome and/or renal insufficiency. The patients were separated into two groups on the basis of age (group I: ≥60 years and group II: <60 years). Outcomes of patients in terms of the requirement of renal replacement therapy and mortality were recorded. Results: In patients with group I, the causes of AA amyloidosis were as follows: FMF 16 (50%), bronchiectasis 7 (23%), chronic osteomyelitis 2 (6%), inflammatory bowel disease 2 (6%), rheumatoid arthritis 2 (6%), ankylosing spondylitis 1 (3%) and unknown aetiology 2 (6%). The underlying disorders of AA amyloidosis in group II patients were as follows: FMF 17 (81%), Behcet’s disease 1 (5%) and unknown aetiology 3 (14%). No statistically significant differences were detected between two groups with regard to systolic and diastolic blood pressures, albumin, proteinuria and lipids. The combination of chronic kidney disease and nephrotic syndrome was the most common clinical presentation in group I (73%) and group II (43%) (p = .05). Compared to the group II, estimated glomerular filtration rate was significantly lower in group I at the time of kidney biopsy (p = .003). At 12-month follow-up, 61% of the group I and 33% of the group II developed end-stage kidney disease requiring dialysis, while 11% of the group I died. Conclusion: Our results indicated that renal AA amyloidosis is a rare disease in advanced age patients. At baseline and follow-up period, advanced age patients had worse kidney disease and outcomes.

Non-Diabetic Kidney Disease in Type 2 Diabetic Patients: Prevalence, Clinical Predictors and Outcomes

Background/Aims: Diabetic kidney disease (DKD) is one of the most frequent microvascular complications of diabetes and is the leading cause of end-stage kidney disease worldwide. In patients with diabetes, non-diabetic kidney disease (NDKD) can also occur. NDKD can be either alone or superimposed with the DKD. In this study, we aimed to investigate the utility of kidney biopsy in patients with type 2 diabetes mellitus (T2DM) and the predictability of diagnosing DKD versus NDKD from clinical and laboratory data. We also evaluated the prevalence and etiology of NDKD in patients with T2DM. Methods: We retrospectively reviewed type 2 diabetic patients who had kidney biopsy in the last 10 years for diagnosing possible NDKD in our center. In all patients kidney biopsies were performed because of atypical clinical features and biopsy samples were examined by light and immunofluorescence microscopy. Clinical parameters, laboratory workup and office blood pressures were recorded for each patient at the time of biopsy. Results: Eight patients were excluded due to missing data. A total of 48 patients (female/male: 26/22 and mean age: 59±8 years) were included in the study. According to the biopsy findings, 24 (50%) patients had NDKD alone, 20 (41.7%) had DKD alone and 4 (8.3%) had coexisting DKD and NDKD. The most common NDKD diagnoses were membranous nephropathy (29.2%), tubulointerstitial nephritis (20.8%) and IgA nephropathy (12.5%). There were no significant differences in three groups with respect to the duration of diabetes, proteinuria, hematuria and glycated hemoglobin A1c levels. Diabetic retinopathy (DR) was the most significant finding, which was associated with DKD. Positive and negative predictive values of DR for DKD were 88 and 81%, respectively. Conclusion: This study demonstrated a high prevalence of NDKD in patients with T2DM. The absence of DR strongly predicted NDKD. Clinical decision alone can lead to wrong diagnosis and delay in appropriate therapy. Clinicians should consider the kidney biopsy more liberally when there is uncertainty on the exact etiology of the kidney disease. However, prospective multicenter studies are needed to clarify the prognosis and outcomes of patients with diabetics.

Urothelial carcinoma of the allograft kidney developed in a renal transplant patient

Renal transplantation is the best option in the treatment of end-stage renal disease However these patients are under the risk of developing malignancies particularly due to effects of immune supression. These malignancies tend to be more agressive compared to the general population. Here, we present a case of urothelial carcinoma develoing in the ureter of allograft kidney.