Blood pressure response to exercise in unaffected relatives of autosomal dominant polycystic kidney disease patients: an observational study.

INTRODUCTION: Hypertension is an early finding of autosomal dominant polycystic kidney disease (ADPKD) and is related to different mechanisms. Cyst expansion-related renin secretion or early endothelial dysfunctions are some of these hypotheses. In addition, the underlying genetic factor is thought to play a role in the inheritance of hypertension. The differential course of hypertension in ADPKD preoccupies that relatives of ADPKD patients may also be at risk for this underlying mechanisms with a genetically determined abnormal endothelial-vascular state. In this study, we aimed to evaluate blood pressure response to exercise as an initial vascular problem in unaffected and normotensive relatives of hypertensive ADPKD patients. METHODS: This is an observational study including unaffected and normotensive relatives (siblings and children) of ADPKD patients (relative group) and healthy controls (control group) who performed an exercise stress test. A 6-lead electrocardiogram was recorded and blood pressure was measured automatically with a cuff worn on the right arm, immediately before the test and every 3 min during the exercise and the recovery phase. Participants continued the test until their age-specific target heart rate was reached or symptoms occurred that required discontinuation of the test. The highest blood pressure and pulse values during exercise were noted. In addition, as a marker for endothelial function, nitric oxide (NO) and asymmetric dimethylarginine (ADMA) levels were measured at baseline and post-exercise. RESULTS: There were 24 participants in the relative group (16 female, mean age 38.45 years) and 30 participants in the control group (15 female, mean age 37.96 years). Two groups were similar in terms of age, gender, body mass index (BMI), smoking status, resting systolic blood pressure (SBP)/diastolic blood pressure (DBP) and biochemical parameters. Mean SBP and DBP were similar in both groups during 1st, 3rd and 9th minutes of exercise (1st minute: 136.25 ± 19.71 mmHg vs 140.36 ± 30.79 mmHg for SBP, p = 0.607, 84.05 ± 14.75 mmHg vs 82.60 ± 21.60 mmHg for DBP, p = 0.799; 3rd minute: 150.75 ± 30.39 mmHg vs 148.54 ± 27.30 mmHg for SBP, p = 0.801, 98.95 ± 26.92 mmHg vs 85.92 ± 17.93 mmHg for DBP, p = 0.062; 9th minute: 156.35 ± 30.84 mmHg vs 166.43 ± 31.90 mmHg for SBP, p = 0.300, 96.25 ± 21.99 mmHg vs 101.78 ± 33.11 mmHg for DBP, p = 0.529 for control and relatives, respectively). During the recovery phase, SBP decreased in both groups in 6th minute (119.85 ± 14.06 mmHg vs 122.86 ± 16.76 mmHg, p = 0.538 for control and relatives respectively); however, in the relatives of ADPKD patients DBP remained high at the end of the 6th minute (78.95 ± 11.29 mmHg vs 86.67 ± 9.81 mmHg p = 0.025 for control and relatives, respectively). Baseline and post-exercise NO and ADMA levels were similar in both groups (Baseline p = 0.214 and p = 0.818, post-exercise p = 0.652 and p = 0.918 for NO and ADMA, respectively). CONCLUSION: Abnormal blood pressure response to exercise was observed in unaffected normotensive relatives of ADPKD. Although its clinical significance needs to be demonstrated by additional research, it is an important finding that unaffected relatives of ADPKD may be at risk for an altered arterial vascular network. Furthermore, these data are the first to demonstrate that relatives of ADPKD patients may also be under risk with a genetically determined abnormal vascular state.

Occult Adrenal Insufficiency in Renal Amyloidosis Patients.

OBJECTIVE: Systemic amyloidosis may affect many organs, and may cause endocrinologic problems which may result in adrenal insufficiency. However, assessment of adrenocortical reserve is challenging in amyloidosis patients with renal involvement. We aimed to evaluate adrenocortical reserve with various methods of cortisol measurement to determine any occult clinical condition. METHODS: Patients with renal amyloidosis and healthy subjects were evaluated in this cross-sectional study. Basal cortisol, corticosteroid-binding globulin (CBG), and albumin levels were measured. Serum free cortisol (cFC) level was calculated. Cortisol response tests performed after ACTH stimulation test (250 µg, intravenously) were evaluated, and free cortisol index (FCI) was calculated. RESULTS: Twenty renal amyloidosis patients, and 25 healthy control subjects were included in the study. Patients and control subjects had similar median serum baseline cortisol levels [258 (126-423) vs 350 (314-391) nmol/L, p=0.169)] whereas patients' stimulated cortisol levels at the 60th minute were lower [624 (497-685) vs 743 (674-781) nmol/L, p=0.011)]. The 60th-minute total cortisol levels of 8 of the 20 (40%) amyloidosis patients were <500 nmol/L, but only three of these 8 patients had stimulated FCI <12 nmol/mg suggesting an adrenal insufficiency (15%). CONCLUSION: ACTH stimulation test and cortisol measurements should be considered in renal amyloidosis patients with severe proteinuria to avoid false positive results if only ACTH stimulation test is used. It will be appropriate to evaluate this group of patients together with estimated measurements as FCI.

Tacrolimus intrapatient variability in BK virus nephropathy and chronic calcineurin toxicity in kidney transplantation.

Intrapatient variability (IPV) in tacrolimus has been increasingly acknowledged as a risk factor for poor graft survival after kidney transplantation. Although past studies have mainly accounted for IPV in acute or chronic rejection states as due to underimmunosuppression, this is not yet clear. So far, tacrolimus IPV for BK virus-associated nephropathy (BKVN) and chronic calcineurin inhibitor toxicity (CNIT) has not been investigated. Here, we evaluated IPV in tacrolimus for BKVN and chronic CNIT, which are mainly considered as overimmunosuppression states. In this case-control study, kidney allograft biopsies conducted between 1998 and 2018 were included, with patients grouped by biopsy results as BKVN alone group, CNIT alone group, and normal graft function (control group). IPV was estimated as mean absolute deviation. Our study groups included 25 kidney transplant recipients with BKVN alone, 91 patients with CNIT alone, and 60 patients with normal 5-year graft survival (control group). In analyses of IPV in tacrolimus six months before graft biopsy, IPV was highest in the BKVN group (P = 0.001). The BKVN group also had the highest IPV in tacrolimus at 12 months after biopsy (P = 0.001), with all pairwise comparisons statistically different between groups. At 12 months after biopsy, five patients (20%) in the BKVN group and 10 patients (10.9%) in the CNIT group had graft loss. Among other risk factors, BKVN and chronic CNIT are consequences related to high IPV. Quantification of IVP for tacrolimus in clinical practice would help to optimize kidney transplant outcomes.

Urinay neutrophil gelatinase-associated lipocalin as a biomarker in different renal problems

Background/aim: Neutrophil gelatinase-associated lipocalin (NGAL) is used previously to estimate the etiology, severity, and clinical outcomes of acute kidney injury (AKI). However, the role of urinary NGAL (uNGAL) in the postrenal setting is not clear. In our study, we aimed to discover the cut-off value of uNGAL that can be used in the differential diagnosis of underlying AKI etiologies. Materials and methods: In this prospective cross-sectional study, we examined 82 subjects in four groups: patients that had (1) postrenal AKI; (2) AKI other than postrenal etiologies; (3) stable chronic kidney disease; and (4) healthy subjects. A renal function assessment was carried out by measuring serum creatinine (sCr) and uNGAL at the time of diagnosis [0th min (T0)]. We followed the study group for three months. Results: At the time of diagnosis, sCr (T0) was highest in the postrenal AKI and AKI groups in contrast to stable chronic kidney disease patients and healthy subjects (P < 0.001), as expected. T0 median uNGAL was highest in the postrenal group (P < 0.001). Area under curve (AUC) of uNGAL to estimate postrenal AKI presence was 0.957 (95% CI, 0.897­1.000; P < 0.001). The cut-off point of uNGAL was 42.625 ng/mL for this estimation. Conclusion: Patients with AKI must be classified according to the underlying etiologies as soon as possible. uNGAL may be useful to estimate the etiologies, and whether the problem is acute or chronic in the course. In postrenal kidney problems, to plan the urgency of the urologic procedures, it is crucial.

Risk Factors of Antibody-Mediated Rejection and Predictors of Outcome in Kidney Transplant Recipients.

OBJECTIVES: Kidney transplant is the treatment of choice for patients with end-stage renal disease. Antibody-mediated rejection is associated with higher rates of graft loss in kidney transplant recipients. Determining the risk factors of antibody-mediated rejection is vital for its prevention, early diagnosis, and appropriate treatment, as these factors may be important in maintaining long-term graft survival in transplant recipients. In our study, we analyzed the risk factors of antibody-mediated rejection in kidney transplant recipients and the negative impact of antibody-mediated rejection on graft function. MATERIALS AND METHODS: We analyzed demographic and clinical data of 124 kidney transplant recipients (37 female [30%] and 87 male [70%] patients) who were diagnosed with antibody-mediated rejection at transplant biopsy. We compared graft outcomes of this patient cohort versus 75 kidney transplant recipients (24 female [32%] and 51 male [68%] patients) who were not diagnosed with antibody-mediated rejection. RESULTS: Mean ages of patients with and without antibody-mediated rejection were 38.2 ± 13.6 and 34.4 ± 13.0 years, respectively. Mean ages of donors for patients with antibody-mediated rejection was significantly higher (48.0 ± 13.2 y) than for donors of patients without antibody-mediated rejection (47.1 ± 11.4 y; P < .05). Rate of graft loss was 15.3% in patients with antibody-mediated rejection; patients without antibody-mediated rejection had no graft loss (P < .05). Positive panel reactive antibody levels and blood transfusion before transplant were found to be risk factors of antibody-mediated rejection in kidney transplant recipients. However, recipients who received tacrolimus had less antibody-mediated rejection episodes than recipients who received sirolimus or cyclophosphamide. CONCLUSIONS: Antibody-mediated rejection is associated with high rates of graft loss in kidney transplant recipients. Avoiding blood transfusion, lowering panel reactive antibody levels, choosing younger donors, and using tacrolimus in high-risk kidney transplant recipients may reduce antibody-mediated rejection rates and provide better graft survival.

The effect of Helicobacter pylori eradication on proteinuria in patients with primary glomerulonephritis.

INTRODUCTION: Glomerulonephritis is still the primary cause among the diseases causing end stage renal disease. Helicobacter pylori (HP), also having a local proinflammatory effect on gastric mucosa, can trigger a local and systemic inflammatory response, and consequently have a role in the development of extragastrointestinal defects. MATERIAL AND METHODS: The study was composed of patients diagnosed with primary glomerulonephritis who had dyspeptic complaints throughout the diagnosis. Patients who received endoscopic biopsy upon the determination of pathologic findings in their upper gastrointestinal endoscopy were HP positive in their biopsy material. A triple eradication therapy was initiated for HP. RESULTS: The study included 14 female and 19 male patients, 33 in total, whose biopsy material was determined to be HP positive. Before the eradication for HP, we found serum albumin to be 34.0 (19.0-51.0) g/l, serum total protein 58.6 ±12.9 g/l, serum creatinine 0.9 (0.5-1.2) and proteinuria 3069 (652-12392) mg/day in 24-hour urine. After the eradication, however, serum albumin was found to be 40 (20-52) g/l, serum total protein 62.3 ±11.1 g/l, serum creatinine 1.02 (0.6-1.29) mg/dl and proteinuria was 2850 (172-15181) mg/day in 24-hour urine. A comparison of the results showed that a statistically significant difference is established between the serum albumin, total protein and creatinine values (p = 0.001, p = 0.001 and p = 0.021, respectively), but not between proteinuria values in 24-hour urine (p = 0.990). CONCLUSIONS: Patients with primary glomerulonephritis, HP eradication treatment has an effect on serum albumin levels.

Unknown aspect of the old disease: does dyslipidemia in systemic AA amyloidosis differ from the dyslipidemia in primary glomerulonephritis?

AIM: To investigate the nature of dyslipidemia and its diversity in patients with systemic AA amyloidosis. METHODS: The reports of the kidney biopsies performed due to nephrotic proteinuria (>3.5 g/day/1.73 m(2)) with preserved renal function [glomerular filtration rate (GFR) >60 mL/min/1.73 m(2)] were reviewed. Clinical and laboratory data of the patients with systemic AA amyloidosis and primary glomerulonephritis (PG) were analyzed. RESULTS: A total of 104 (systemic AA amyloidosis: 43, PG: 61) patients were included in the study. Proteinuria and GFR levels were similar in both the groups. Patients with systemic AA amyloidosis group had lower serum albumin (p = 0.002), lower hemoglobin levels (p = 0.001), higher platelet counts (p = 0.002) and higher C-reactive protein levels (p = 0.001) compared to patients in PG group. Although the frequency of dyslipidemia was similar in the groups (86.0 vs. 93.4%), patients with systemic amyloidosis had both lower values of LDL-C (4.56 ± 2.05 vs. 5.49 ± 2.23 mmol/L, p = 0.028) and HDL-C (1.19 ± 0.36 vs. 1.35 ± 0.39 mmol/L, p = 0.035). Serum lipid levels were correlated with serum total protein, albumin and proteinuria levels in PG group. However, in the systemic amyloidosis group, only one clear correlation between serum lipid and hemoglobin levels was estimated. A multivariate analysis demonstrated that LDL-C was independently associated with the etiology of nephrotic proteinuria, serum total protein, serum albumin (inversely) and hemoglobin levels. CONCLUSIONS: Although dyslipidemia is closely associated with serum total protein, albumin and proteinuria in patients with PG, there is no clear such association in patients with systemic amyloidosis. Correlation between serum lipid and hemoglobin levels in this group and other findings point out that probably complex mechanisms take place in dyslipidemia of nephrotic syndrome caused by systemic AA amyloidosis.

Prognostic factors in crescentic glomerulonephritis: a single-center experience.

INTRODUCTION: Crescentic glomerulonephritis (CGN) is a fatal disease, rapidly leading to end-stage renal disease. Diagnosis should be accurate and treatment should be started immediately. We investigated the factors associated with the renal prognosis in CGN patients. MATERIALS AND METHODS: Forty-one patients with CGN who were followed up at the Nephrology Clinic of Ankara Numune Education and Research Hospital were divided into 2 arms of the dialysis-dependent group after treatment and the group that was followed up without dialysis. Demographic and clinical features along with biopsy findings during time of diagnosis were evaluated for both groups. RESULTS: The mean age was 41.3 ± 17.2 years old and 26 were men. Twenty patients developed end-stage renal disease, requiring long-term dialysis. The dialysis-dependent group had higher serum creatinine levels (8.2 ± 3.6 mg/dL versus 2.6 ± 2.5 mg/dL) and percentages of glomeruli with crescent (83.1 ± 19.1% versus 56.4 ± 11.9%), were more likely to have oligoruia-anuria (90.5% versus 9.5%) and be dialysis-dependent at admission (86.4% versus 13.6%), and had longer elapsed time until the beginning of treatment (18.9 ± 10.4 days versus 10.6 ± 3.0 days) after treatment. At admission, their serum creatinine was greater than 4.2 mg/dL and the rate of crescentic glomeruli was greater than 63%. CONCLUSIONS: In patients with CGN, renal prognosis is poor and the time of admission to the hospital, degree of renal insufficiency, presence of oligo-anuria, dialysis requirement, and the percentage of crescentic glomeruli on biopsy are closely related to progression to end-stage renal disease.

Coexistence of autosomal dominant polycystic kidney disease and amyloidosis in a patient with nephrotic-range proteinuria.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by the development and growth of cysts in the kidneys. Non-nephritic-range proteinuria is a common presentation in ADPKD patients; however, nephrotic syndrome is a rare coincidence. A 52-year-old man is described who was diagnosed with secondary amyloidosis with ADPKD. To our knowledge, this is the first case of amyloidosis associated with frequently infected renal cysts. Patients with ADPKD who show massive proteinuria should be investigated in terms of concomitant glomerular disease.

Evaluation of the mean platelet volume in secondary amyloidosis due to familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an inflammatory disorder that is leading cause of secondary amyloidosis (AA). This study was designed to investigate the level of mean platelet volume (MPV) in AA. Seventy-four FMF, 29 AA patients and 180 healthy controls, were included. There was no significant difference between the cases in terms of sex and age. MPV levels were measured in all groups. In the FMF group, MPV level was significantly higher when compared to the control group. MPV level was significantly lower in AA group in comparison with the FMF and healthy control groups. In summary, our present study showed low MPV values in AA due to FMF.

Revisiting secondary amyloidosis for an inadequately investigated feature: dyslipidemia.

Secondary amyloidosis is the most frequent form of the systemic amyloidosis around the world. Data on frequency and nature of dyslipidemia in patients with secondary amyloidosis are not conclusive. We evaluated the lipid abnormalities and their association with clinical and laboratory characteristics of the patients with secondary amyloidosis. The reports of the kidney biopsies performed in our hospital were reviewed. Clinical and laboratory data of the patients with biopsy-proven secondary amyloidosis were analyzed retrospectively. A total of 102 patients were diagnosed as having secondary amyloidosis. Familial Mediterranean fever was the leading cause of secondary amyloidosis accounting for 42.2 % of the cases. The most frequent indication for kidney biopsy was the nephrotic range proteinuria. The most common clinical and laboratory characteristics at the time of the diagnosis were edema, proteinuria and impaired renal function. The frequency of the nephrotic range proteinuria and microscopic hematuria were 75.5 and 18.6 %, respectively. Dyslipidemia was found in 88 % of the cases. Serum lipids significantly correlated with estimated glomerular filtration rate (eGFR), but not with serum albumin or urine protein levels. We demonstrated that majority of the patients with secondary amyloidosis had serum lipid abnormalities. Dyslipidemia was closely associated with GFR in a manner that patients with advanced stage kidney disease had lower serum lipid levels.

Acute thrombotic thrombocytopenic purpura following orthopedic surgery: case report and review of the literature.

Thrombotic thrombocytopenic purpura (TTP) is an uncommon cause of hematological and renal abnormalities in the postoperative period. An association between TTP and orthopedic surgery, a rare entity, has been reported in the literature. It has the strong possibility of being fatal and therefore should be treated immediately, mostly by plasmapheresis. We report a 15-year-old girl of TTP following a high tibial valgus osteotomy (HTO).