Chronic Kidney Disease Risk in Living Kidney Transplant Donors: A Long-Term Follow-Up Study.

BACKGROUND: Living kidney donors (LKD) may experience some untoward consequences following donation such as development of chronic kidney disease (CKD). In this study, we aimed to investigate the rate of development of CKD and factors affecting the development of CKD in LKDs during long-term follow-up from a center in Turkey. METHODS: This study was a retrospective analysis of LKDs followed between January 2000 and December 2017. Pre-transplant and post-transplant clinical data of the 338 LKDs were recorded and compared. Factors affecting the development of stage 3 and later stages of CKD were analyzed. RESULTS: Majority of the donors were females (64.2%), and the median age of all donors was 47 (39-54) years. Stage 3 CKD developed in 50 donors during the median follow-up of 71 months. Older age at the time of transplantation and a low pre-transplant estimated glomerular filtration rate (eGFR) were determined as the factors affecting the development of stage 3 CKD (p < 0.001, p < 0.001). The receiver operating characteristic analysis showed that the cut-off age for the development of stage 3 CKD was 50.5 years. Newly diagnosed hypertension was detected in 57 patients (16.8%) after the transplantation. While hypertension was seen at a rate of 42% in those with an eGFR <60 mL/min/1.73 m2, it was detected at 19.4% in the group with an eGFR >60 mL/min/1.73 m2 (p < 0.001). CONCLUSION: These results reveal that being a LKD is associated with the development of CKD and hypertension. Age and eGFR values at the time of transplantation were the determinants for the development of CKD.

A comparative urinary proteomic and metabolomic analysis between renal aa amyloidosis and membranous nephropathy with clinicopathologic correlations.

Urinary omics has become a powerful tool for elucidating pathophysiology of glomerular diseases. However, no urinary omics analysis has been performed yet on renal AA amyloidosis. Here, we performed a comparative urine proteomic and metabolomic analysis between recently diagnosed renal AA amyloidosis (AA) and membranous nephropathy (MN) patients. Urine samples of 22 (8 AA, 8 MN and 6 healthy control) patients were analyzed with nLC-MS/MS and GC/MS for proteomic and metabolomic studies, respectively. Pathological specimens were scored for glomerulosclerosis and tubulointerstitial fibrosis grades. Functional enrichment analysis between AA and control groups showed enrichment in cell adhesion related sub-domains. Uromodulin (UMOD) was lower, whereas ribonuclease 1 (RNase1) and α-1-microglobulin/bikunin precursor (AMBP) were higher in AA compared to MN group. Correlations were demonstrated between UMOD-proteinuria (r = -0.48, p = 0.03) and AMBP-eGFR (r = -0.69, p = 0.003) variables. Metabolomic analysis showed myo-inositol and urate were higher in AA compared to MN group. A positive correlation was detected between RNase1 and urate independent of eGFR values (r = 0.63, p = 0.01). Enrichment in cell adhesion related domains suggested a possible increased urinary shear stress due to amyloid fibrils. UMOD, AMBP and myo-inositol were related with tubulointerstitial damage, whereas RNase1 and urate were believed to be related with systemic inflammation in AA amyloidosis. SIGNIFICANCE: Urinary omics studies have become a standard tool for biomarker studies. However, no urinary omics analysis has been performed yet on renal AA amyloidosis. Here, we performed a comparative urinary omics analysis between recently diagnosed renal AA amyloidosis (AA), membranous nephropathy (MN) patients and healthy controls. Pathological specimens were scored with glomerulosclerosis (G) and tubulointerstitial fibrosis (IF) grades to consolidate the results of the omics studies and correlation analyzes. Functional enrichment analysis showed enrichment in cell adhesion related sub-domains due to downregulation of cadherins; which could be related with increased urinary shear stress due to amyloid deposition and disruption of tissue micro-architecture. In comparative proteomic analyzes UMOD was lower, whereas RNase1 and AMBP were higher in AA compared to MN group. Whereas in metabolomic analyzes; myo-inositol, urate and maltose were higher in AA compared to MN group. Correlations were demonstrated between UMOD-proteinuria (r = -0.48, p = 0.03), AMBP-eGFR (r = -0.69, p = 0.003) and between RNase1-Urate independent of eGFR values (r = 0.63, p = 0.01). This study is the first comprehensive urinary omics analysis focusing on renal AA Amyloidosis to the best of our knowledge. Based on physiologic roles and clinicopathologic correlations of the molecules; UMOD, AMBP and myo-inositol were related with tubulointerstitial damage, whereas RNase1 and urate were believed to be increased with systemic inflammation and endothelial damage in AA amyloidosis.

Dismal Prognosis of Acute Allergic Tubulointerstitial Nephritis in Patients with AA Amyloidosis.

INTRODUCTION: Patients with AA amyloidosis may present with acute kidney injury that progresses to end-stage kidney disease in a short period of time. Acute allergic tubulointerstitial nephritis (aTIN) is a frequent cause of acute kidney injury in patients with AA amyloidosis. Although aTIN has a favorable prognosis in the general population, the course of aTIN in patients with AA amyloidosis was not previously reported. In this retrospective study, we determined the prognosis of aTIN superimposed on AA amyloidosis. METHODS: Thirty-two patients with combined pathological diagnosis of AA amyloidosis + aTIN and 32 patients with isolated aTIN were compared in terms of 1-year renal functions after the biopsies were performed with an indication of acute kidney injury. Baseline renal functions and number of patients requiring hemodialysis at the time of biopsy was similar in both groups. RESULTS: At the end of the 12-month follow-up period, 29 of 32 patients in the amyloidosis + aTIN group and 1 of 32 patients in the isolated aTIN group required dialysis. Most of these patients with AA amyloidosis had completely normal renal function before the episode of acute kidney injury and had clear exposures to drugs associated with aTIN. CONCLUSION: In contrary to the patients without AA amyloidosis, patients with AA amyloidosis have extremely high risk of permanent renal failure in case of development of aTIN. Great caution should be exercised in prescribing drugs that are associated with aTIN, in patients with AA amyloidosis.

Petroselinum crispum, a commonly consumed food, affects sirolimus level in a renal transplant recipient: a case report.

Sirolimus is an immunosuppressive drug used to prevent graft rejection. Therapeutic drug monitoring is required as with other immunosuppressive drugs. Previous studies have shown the interactions between sirolimus and drugs that affect the activity of cytochrome P450 3A4 and P-glycoprotein. There is an increasing tendency for the use of herbal remedies in many countries. Medicinal herbs are rich sources of natural bioactive compounds that could interact with drugs. Parsley, Petroselinum crispum, is a food, spice, and also a medicinal herb. We report a case of a renal transplant recipient who had a supratherapeutic blood level of sirolimus due to consuming excessive parsley to highlight a possible herb-drug interaction. This is the first case report describing sirolimus-parsley interaction. Herb-drug interactions are especially important for drugs with a narrow therapeutic window. For this reason, healthcare professionals should question all patients, especially transplant patients, about the use of herbs or herbal products and report interactions. PLAIN LANGUAGE SUMMARY: Parsley, a commonly consumed food, affects the level of an important drug in a renal transplant recipient: A case report Sirolimus is a drug that suppresses the immune response used to prevent organ rejection in people who have had kidney transplants. In order to reach the optimum balance between therapeutic efficacy and adverse effects, sirolimus blood levels should be closely monitored. Previous studies have shown the interactions between sirolimus and drugs that affect the activities of metabolizing enzymes and transporter proteins. Parsley is a food, spice, and also a medicinal herb. Medicinal herbs are rich sources of natural bioactive compounds that could interact with a prescription drug. We report a case of a renal transplant recipient who had a rise in the blood level of sirolimus due to the ingestion of an excessive amount of parsley to highlight possible herb-drug interaction.

Mean platelet volume in familial Mediterranean fever related AA amyloidosis and comparison with common primary glomerular diseases

Background/aim: Compared to healthy controls, mean platelet volume (MPV) is frequently higher in patients with Familial Mediterranean fever (FMF) but lower in AA amyloidosis patients. The reason for the difference in MPV levels in FMF patients with and without AA amyloidosis is unclear. The aim of the study was to determine whether low MPV is unique to AA amyloidosis or MPV is similarly low in all glomerular diseases as a result of proteinuria and/or renal dysfunction. Materials and methods: We compared pre-biopsy MPV levels of patients with AA amyloidosis secondary to FMF, to MPV levels of patients with membranous glomerulonephritis, focal segmental glomerulosclerosis (FSGS) and IgA nephropathy that all present with proteinuria and renal dysfunction. Results: 703 patients (411 male, 292 female) were included in the study. Mean age was 42.6  14.3 years. There were 124 patients with AA amyloidosis, 224 patients with IgA nephropathy, 188 patients with membranous glomerulonephritis, and 167 patients wit h FSGS. Patients with AA amyloidosis had lower MPV levels compared to patients without AA amyloidosis (7.9  1.2 fL vs. 8.2  0.9 fL respectively, p = 0.008). Patients with AA amyloidosis had significantly lower MPV compared to patients with each of the othe r diagnoses. Independent predictors of MPV were platelet count (ß = ­0.321, p < 0.001) and CRP (ß = ­ 0.134, p < 0.03). Conclusion: This study is the largest study of MPV in patients with biopsy proven AA amyloidosis and confirms previous studies reporting low MPV in AA amyloidosis. This study indicates that low MPV in AA amyloidosis cannot be explained with proteinuria and renal dysfunction.

A case report of tigecycline induced acute pancreatitis in a renal transplant patient and review of the literature: Should we avoid tigecycline in patients on calcineurin inhibitors?

Tigecycline has been approved by the US (United States) Food and Drug Administration in a variety of complicated infections due to its broad-spectrum antibiotic activity. Following phase III trials, the product label was revised and acute pancreatitis was listed as an adverse effect. Its safety profile in special groups such as renal transplant patients is not exactly known. We report the first case of unintentional rechallenge of tigecycline induced pancreatitis in a renal transplant patient. Ten days following the renal transplantation, a 35-year-old patient presented to the clinic with acute rejection. He received anti-thymocyte globulin (ATG) and pulse steroid treatments for rejection. Following the treatment, he developed perianal cellulitis and tigecycline was started. Nine days following initiation of tigecycline he received thrombectomy for his incidental cardiac thrombus. One day after thrombectomy, he developed acute pancreatitis (AP). Thrombectomy was suspected to be the cause of AP. During hospitalization for transplant rejection, tigecycline was re-started for a newly developed complicated abdominal infection. On the third day of the tigecycline re-treatment, he developed a second episode of AP. Following tigecycline withdrawal, his symptoms resolved and serum pancreatic enzymes returned to normal, thus AP was ultimately attributed to tigecycline. This lethal side effect should be kept in mind while treating severe infections in renal transplant recipients.

Renal Lymphangiomatosis Mimicking Polycystic Kidney Disease In An Adult, A Case Report and Literature Review.

Renal lymphangiomatosis is an unusual disorder. It may develop due to the abnormality of the intrarenal, peripelvic and perirenal lymphatics. The differential diagnosis contains renal lymphoma, polycystic kidney disease, multicystic dysplasia and renal tumors. We report a case of renal lymphangiomatosis, previously diagnosed as autosomal dominant polycystic kidney disease, to emphasize that these two diseases can be easily confused. It should be kept in mind that RL is in the differential diagnosis of polycystic renal disease to prevent overtreatment.

Donor Nephrectomy May Compromise the Cardiovascular System: A Retrospective, Single-Center Study.

OBJECTIVES: Our goal was to determine the short-term effects of donor nephrectomy on the cardiovascular system and to gain a better understanding of the recently recognized long-term increased risk of end-stage renal disease and cardiovascular mortality. MATERIALS AND METHODS: Living kidney donors who underwent donor nephrectomy between January 2010 and January 2015 at the Hacettepe University Transplantation Unit were retrospectively screened. Echocardiographic parameters, kidney volumes, and renal functions before nephrectomy were compared with measurements after nephrectomy. Flow-mediated dilatation values of living kidney donors were compared with healthy individuals. RESULTS: The study included 73 female and 31 male living kidney donors with a mean age of 46.1 ± 10.8 years. In the comparative analysis of donors versus 35 healthy individuals, the changes in flow-mediated dilatation were 12.3 ± 5.7% and 15.4 ± 6.3%, respectively (P = .016). In the comparative analysis of preoperative versus the last visit transthoracic echocardiographic results, left ventricular end-systolic and end-diastolic diameters decreased and left ventricular posterior wall thickness and septum thickness increased (P = .025, P = .002, P = .026, and P = .019, respectively). CONCLUSIONS: Nephrectomy may cause several hemodynamic changes in living kidney donors, which may exacerbate cardiovascular risks in this population.

Assessment of Clinically Relevant Drug Interactions by Online Programs in Renal Transplant Recipients.

BACKGROUND: Potential drug-drug interactions (pDDIs) with immunosuppressive drugs are frequently observed in renal transplant recipients. Drug interaction programs are acknowledged as a fundamental tool to alert physicians to pDDIs, but there is a high concern about variation among different programs in terms of quality and reliability of information. OBJECTIVES: To (a) characterize the difference in severity levels of pDDIs with tacrolimus and cyclosporine provided by 3 drug interaction programs and (b) identify clinically relevant DDIs with these immunosuppressive drugs in renal transplant recipients. METHODS: This study was conducted in a nephrology outpatient clinic at the University Research & Training Hospital between November 2017 and February 2018. A clinical pharmacist attended clinic visits with physicians and evaluated drug interactions. Micromedex, Medscape, and Lexicomp drug interaction programs were used to identify pDDIs and their severities. Furthermore, Drug Interaction Probability Scale (DIPS) criteria were applied to identify clinically relevant drug interactions seen in clinic patients. Finally, a clinical pharmacist intervened to manage clinically relevant drug interactions identified by DIPS. RESULTS: 80 patients (54 under tacrolimus; 26 under cyclosporine treatment) were included in this study. The 3 drug interaction programs generated 648 pDDIs, 63 of which were different drug interaction pairs. Ninety-eight pDDIs were common to all 3 drug interaction programs. Sixty-three different drug interaction pairs were evaluated according to severity level, and 3 drug interaction pairs were at the same level (moderate) among the programs. The Fleiss' kappa overall interrater agreement was poor. The kappa revealed a moderate agreement for interaction pairs with a "severe" rating and a slight agreement for interaction pairs with a "major" rating. According to the DIPS evaluation, 11 pDDIs were classified as "possible," and the percentage of clinically relevant drug-drug interactions was 4.0% (10/248), 4.2% (11/265), and 8.2% (11/135) for Medscape, Lexicomp, and Micromedex, respectively. Although daily doses of immunosuppressive drugs were not changed, the blood concentrations of these drugs increased after administration of an interacting drug. As a result, in order to maintain normal therapeutic range of concentrations, dose reduction or drug change was applied where appropriate. CONCLUSIONS: Interaction checker programs are commonly used by health institutions, since they provide quick and summarized information on mechanism and management of drug interactions, when no clinical pharmacist is present to interpret. However, the likelihood of detecting clinically relevant DDIs by interaction checker programs is relatively low, and there are inconsistencies among different programs. Individualized patient monitoring should be maintained by a multidisciplinary health care team that includes a clinical pharmacist, and decision making should be based on professional assessment of the renal transplant patient. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest to disclose.

Effect of Local Polyhexanide Application in Preventing Exit-Site Infection and Peritonitis: A Randomized Controlled Trial.

Topical antibiotic and antiseptic agents have been documented to reduce exit-site infection (ESI) and peritonitis in PD. The aim of this randomized controlled study was to evaluate the efficacy of polyhexanide in the prevention of ESI and peritonitis. Patients were excluded if they had active infection, > 18 years of age, ESI and peritonitis within the previous 4 weeks, received PD for less than 3-months and history of allergy to either drug. All patients were followed up until catheter removal, death, switch to dialysis, transplantation or the end of the study. ESI, tunnel infection, peritonitis, catheter removal and microorganism cause of catheter-related infection were recorded prospectively during clinic follow-up. A total of 88 patients (41 povidone-iodine group; 47 polyhexanide group) were enrolled with a total follow-up duration of 480 and 555 patient-months for povidone-iodine and alternating group, respectively. There were no significant differences in the age, sex, BMI, time of PD, rate of DM, and S. aureus carriage state. A total of 8 ESI and 25 peritonitis episodes were detected during the study. ESI and peritonitis rates tended to be lower in polyhexanide group compared with the povidone-iodine group (0.06 episodes/patient-year vs. 0.12 episodes/patient-year; 0.26 episodes/patient-year vs. 0.32 episodes/patient-year, respectively), but were not significant statistically. Moreover, catheter removal was similar in both groups (0.04 / patient-year vs. 0.05 / patient-year). Polyhexanide is efficient and safe for the prevention of ESI and peritonitis and it may be used as an alternative procedure for the care of healthy exit sites.

Salt intake is associated with inflammation in chronic heart failure.

BACKGROUND: Chronic Heart Failure (CHF) is highly prevalent and is associated with high morbidity and mortality rates. It has been well established that excessive intake of sodium chloride (salt) induced hypertension in some populations. Although salt seems to induce cardiovascular diseases through elevation of blood pressure, it has also been indicated that salt can induce cardiovascular diseases independently from blood pressure elevation. OBJECTIVES: The present study aimed to evaluate the association between salt consumption and inflammation in CHF patients. PATIENTS AND METHODS: This study was conducted on 86 patients between 18 and 65 years old who were diagnosed with New York Heart Association (NYHA) functional class I and II heart failure. Salt intake was calculated by using 24 hour urine sodium excretion. Besides, the association between inflammation and daily salt intake was evaluated regarding C - reactive protein (CPR), High sensitive CRP (HsCPR), Erythrocyte Sedimentation Rate (ESR), and ferritin and fibrinogen levels using Pearson correlation analysis. RESULTS: Our results showed a statistically significant difference between the low (n = 41) and high (n = 45) salt intake groups in terms of serum HsCRP levels (5.21 ± 2.62 vs. 6.36 ± 2.64) (P < 0.048). Additionally, a significant correlation was observed between the amount of salt consumption and HsCRP levels. In this study, daily salt consumption of the enrolled patients was 8.53 gram/day. The medications and even the blood pressures were similar in the two groups, but daily pill count, prevalence of hypertension, and coronary heart disease were higher in the high salt intake group; however, the differences were not statistically significant (P = 0.065). Also, no significant difference was observed between the groups concerning the inflammation markers, such as CRP, ESR, ferritin, and fibrinogen. CONCLUSIONS: Neurohumoral and inflammatory factors are thought to contribute to high mortality and morbidity rates in CHF. Yet, inflammatory markers may early diagnose CHF and predict the prognosis. Excessive salt intake also worsens the inflammation as well as volume control.

MEFV gene mutations in a patient with eosinophilic gastroenteritis.

Eosinophilic gastroenteritis (EG) is an uncommon gastrointestinal disease affecting both children and adults. The underlying molecular mechanism predisposing to the clinical manifestation of eosinophilic gastroenteritis is unknown. A 39-year-old man who was followed up with the diagnosis of familial Mediterranean fever (FMF) was admitted to our clinic with diarrhea, abdominal pain, and weight loss. After endoscopic and colonoscopic examinations EG was diagnosed by histopathological examination. Symptoms were resolved with the treatment of budesonide. To our knowledge, this is the first reported case of EG with the MEFV gene mutations in the literature.