Advanced myocardial tissue characterisation by a multi-component CMR protocol in patients with rheumatoid arthritis.

OBJECTIVES: Rheumatoid arthritis (RA) patients are at increased risk of suffering from adverse cardiovascular events. Cardiovascular magnetic resonance (CMR) mapping techniques might be appropriate tools to complement late gadolinium enhancement (LGE) for the assessment of myocardial involvement. This study aimed to perform advanced myocardial tissue characterisation in RA patients by a multicomponent CMR protocol. METHODS: 22 RA patients were prospectively enrolled and underwent CMR, including LGE and T1/T2 mapping sequences; 20 volunteers served as controls. RESULTS: Mean LV-EF was 66%; prevalence of LGE was 18%. RA patients had increased native T1 (985 vs. 959 ms, p = 0.03), expanded extracellular volume (ECV) (27 vs. 25%, p = 0.02) and higher T2 values (52 vs. 49 ms, p < 0.001) compared to controls irrespective of the presence of LGE. T2 mapping showed the highest prevalence of values beyond the 95% percentile of controls. CONCLUSION: RA patients demonstrated higher T1, ECV and T2 values compared to controls, with most significant differences for T2. Since these results seem to be independent of the presence of LGE, advanced myocardial tissue characterisation including CMR mapping techniques in addition to LGE-CMR might be useful in the evaluation of myocardial involvement in RA patients. KEY POINTS: • RA patients had higher T1, ECV and T2 values compared to controls. • Most significant differences were observed for T2. • Our results seem to be independent of the presence of LGE. • Mapping might be useful in the evaluation of myocardial involvement in RA.

T1 and T2 mapping for evaluation of myocardial involvement in patients with ANCA-associated vasculitides.

BACKGROUND: Myocardial involvement in AAV patients might be silent, presenting with no or nonspecific symptoms, normal ECG, and preserved left-ventricular ejection fraction (LV-EF). Since up to 50% of deaths in these patients may be due to myocardial involvement, a reliable diagnostic tool is warranted. In contrast to LGE-CMR, which has its strengths in detecting focal inflammatory or fibrotic processes, recent mapping techniques are able to detect even subtle, diffuse inflammatory or fibrotic processes. Our study sought to investigate ANCA (antineutrophil cytoplasmic antibody) associated vasculitides (AAV) patients for myocardial involvement by a cardiovascular magnetic resonance (CMR) protocol, including late gadolinium enhancement (LGE) and mapping sequences. METHODS: Thirty seven AAV patients were prospectively enrolled and underwent CMR imaging. Twenty healthy volunteers served as controls. RESULTS: Mean LV-EF was 64%; LGE prevalence of the AAV patients was 43%. AAV patients had higher median native T1 (988 vs. 952 ms, p < 0.001), lower post-contrast T1 (488 vs. 524 ms, p = 0.03), expanded extracellular volume (ECV) (27.5 vs. 24.5%, p < 0.001), and higher T2 (53 vs. 49 ms, p < 0.001) compared to controls, with most parameters independent of the LGE status. Native T1 and T2 in AAV patients showed the highest prevalence of abnormally increased values beyond the 95% percentile of controls. CONCLUSION: AAV patients demonstrated increased T1, ECV, and T2 values, with native T1 and T2 showing the highest prevalence of values beyond the 95% percentile of normal. Since these findings seem to be independent of LGE, mapping techniques may provide complementary information to LGE-CMR in the assessment of myocardial involvement in patients with AAV.

Gender-Specific Differences in Peritoneal Dialysis.

BACKGROUND/AIMS: Gender-specific differences between patients on renal replacement therapy have so far rarely been investigated. In the present study we aimed to describe gender-specific differences in a large cohort of peritoneal dialysis (PD) patients. METHODS: Clinical information for all patients who started PD at our center has been collected since the start of the PD-program in 1979. We used Cox regression to examine associations between technique failure and gender. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 745 patients (315 women and 430 men with a median age of 57 years; IQR 43-67) started PD between 1979 and 2015 in our center. Women were significantly younger at PD start 54 (40-65) years vs. 58 (47-68) years, p<0.001. Within the last almost 15 years, more man than women started PD, but technical survival rates were significantly better in female compared to men (HR=0.662, CI 95% (0.496-0.885) P=0.005). Cardiovascular events were the main cause of death over the study period in both sexes, but decreased over time. Additionally, death due to PD-associated peritonitis decreased significantly over the three decades in both sexes. CONCLUSIONS: Our data suggest that technical survival rates were significantly better in female compared to men over three decades and death due to cardiovascular events and PD-associated peritonitis decreased significantly over the three decades in both sexes.

Evaluation of myocardial involvement in patients with connective tissue disorders: a multi-parametric cardiovascular magnetic resonance study.

BACKGROUND: Severe arrhythmias or heart failure may be surrogates of myocardial involvement in patients with connective tissue disorders (CTD). However, most patients present with unspecific symptoms, normal ECG, and preserved left ventricular ejection fraction (LV-EF). Therefore, timely diagnosis by an accurate technique is crucial. Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has proven value for the detection of focal processes, but due to the often diffuse character of fibrosis/inflammation in CTD patients, CMR mapping techniques might be of incremental value for the assessment of myocardial involvement. Purpose of this study was to evaluate a multi-parametric CMR protocol as a screening tool for myocardial involvement in CTD patients. METHODS: Forty CTD patients were prospectively enrolled and underwent CMR, twenty healthy volunteers served as control group. RESULTS: Mean LV-EF was 62 %; LGE prevalence was low (18 %). CTD patients had higher native T1 (1008 vs. 962 ms, p = 0.001), lower post contrast T1 (494 vs. 526 ms, p = 0.008), expanded extracellular volume (ECV) (28 vs. 25 %, p = 0.001), and higher T2 values (53 vs. 49 ms, p < 0.001) compared to controls. Among patients with values higher than the 95 % percentile of healthy controls, native T1 and T2 values seem to be the most promising discriminators. CONCLUSION: CTD patients showed higher T1, ECV, and T2 values compared to controls, with most significant differences for native T1 and T2, which seem to be independent of the presence of LGE. Our data suggest that CMR mapping techniques are of incremental value in the detection of myocardial involvement in CTD patients.

Activation of nuclear factor of activated T cells 5 in the peritoneal membrane of uremic patients.

Peritoneal inflammation and fibrosis are responses to the uremic milieu and exposure to hyperosmolar dialysis fluids in patients on peritoneal dialysis. Cells respond to high osmolarity via the transcription factor nuclear factor of activated T cells (NFAT5). In the present study, the response of human peritoneal fibroblasts to glucose was analyzed in vitro. Expression levels of NFAT5 and chemokine (C-C motif) ligand (CCL2) mRNA were quantified in peritoneal biopsies of five nonuremic control patients, five uremic patients before PD (pPD), and eight patients on PD (oPD) using real-time PCR. Biopsies from 5 control patients, 25 pPD patients, and 25 oPD patients were investigated using immunohistochemistry to detect the expression of NFAT5, CCL2, NF-κB p50, NF-κB p65, and CD68. High glucose concentrations led to an early, dose-dependent induction of NFAT5 mRNA in human peritoneal fibroblasts. CCL2 mRNA expression was upregulated by high concentrations of glucose after 6 h, but, most notably, a concentration-dependent induction of CCL2 was present after 96 h. In human peritoneal biopsies, NFAT5 mRNA levels were increased in uremic patients compared with nonuremic control patients. No significant difference was found between the pPD group and oPD group. CCL2 mRNA expression was higher in the oPD group. Immunohistochemistry analysis was consistent with the results of mRNA analysis. CD68-positive cells were significantly increased in the oPD group. In conclusion, uremia results in NFAT5 induction, which might promote early changes of the peritoneum. Upregulation of NFAT5 in PD patients is associated with NFκB induction, potentially resulting in the recruitment of macrophages.

Clinical course and long-term outcome of hantavirus-associated nephropathia epidemica, Germany.

Human infection with Puumala virus (PUUV), the most common hantavirus in Central Europe, causes nephropathia epidemica (NE), a disease characterized by acute kidney injury and thrombocytopenia. To determine the clinical phenotype of hantavirus-infected patients and their long-term outcome and humoral immunity to PUUV, we conducted a cross-sectional prospective survey of 456 patients in Germany with clinically and serologically confirmed hantavirus-associated NE during 2001-2012. Prominent clinical findings during acute NE were fever and back/limb pain, and 88% of the patients had acute kidney injury. At follow-up (7-35 mo), all patients had detectable hantavirus-specific IgG; 8.5% had persistent IgM; 25% had hematuria; 23% had hypertension (new diagnosis for 67%); and 7% had proteinuria. NE-associated hypertension and proteinuria do not appear to have long-term consequences, but NE-associated hematuria may. All patients in this study had hantavirus-specific IgG up to years after the infection.

Impact of long-term steroid therapy on epicardial and pericardial fat deposition: a cardiac MRI study.

BACKGROUND: Increased cardiac fat has been identified as a risk factor for coronary artery disease. Metabolic syndrome is associated with increased cardiac fat deposition. Steroids are known to imitate some effects of metabolic syndrome and are frequently used in patients with rheumatic disorders. Primary aim was to evaluate the impact of long-term steroid use on cardiac fat deposition in patients with rheumatic disorders. In addition, we sought to investigate if this effect might be dose-dependent. METHODS: Patients were enrolled as follows: (1) rheumatic disorder; and (2) long-term steroid therapy, and (3) underwent cardiovascular magnetic resonance (CMR) imaging. Patients were stratified in a high-dose (>7.5 mg prednisone equivalent/day for at least 6 months) and a low-dose steroid group (<7.5 mg prednisone equivalent/day) and compared to steroid-naïve controls without rheumatic disorders. RESULTS: 122 patients were included (n = 61 steroid patients, n = 61 controls). N = 36 were classified as high-dose, n = 25 as low-dose steroid group. Steroid patients showed larger epicardial 5.7 [3.5-9.1] cm(2) and pericardial 13.0 [6.1-26.8] cm(2) areas of fat than controls 4.2 [1.3-5.8] cm(2)/6.4 [1.6-15.4] cm(2), p < 0.001, p < 0.01, respectively. High-dose steroid patients had more epi- and pericardial fat both than controls: 7.2 [4.2-11.1] cm(2) vs. 4.4 [1.0-6.0] cm(2), p < 0.001; 18.6 [8.9-38.2] cm(2) vs. 10.7 [4.7-26.8] cm(2), p < 0.05, and patients in the low-dose steroid group (p < 0.01, p < 0.001, respectively). CONCLUSION: The present data suggest increased cardiac fat deposition in steroid-treated patients with rheumatic disorders. Furthermore, this accumulation of cardiac fat seems to be dose-dependent, pointing towards a cumulative effect of steroids.

Acute kidney injury and tools for risk-stratification in 456 patients with hantavirus-induced nephropathia epidemica.

BACKGROUND: Puumala virus (PUUV) is the most common species of hantavirus in Central Europe. Nephropathia epidemica (NE), caused by PUUV, is characterized by acute kidney injury (AKI) and thrombocytopenia. The major goals of this study were to provide a clear clinical phenotyping of AKI in patients with NE and to develop an easy prediction rule to identify patients, who are at lower risk to develop severe AKI. METHODS: A cross-sectional prospective survey of 456 adult patients with serologically confirmed NE was performed. Data were collected from medical records and prospectively at follow-up visit. Severe AKI was defined by standard criteria according to the RIFLE (Risk, Injury, Failure, Loss, End-stage kidney disease) classification. Fuller statistical models were developed and validated to estimate the probability for severe AKI. RESULTS: During acute NE, 88% of the patients had AKI according to the RILFE criteria during acute NE. A risk index score for severe AKI was derived by using three independent risk factors in patients with normal kidney function at time of diagnosis: thrombocytopenia [two points; odds ratios (OR): 3.77; 95% confidence intervals (CI): 1.82, 8.03], elevated C-reactive protein levels (one point; OR: 3.02; 95% CI: 1.42, 6.58) and proteinuria (one point; OR: 3.92; 95% CI: 1.33, 13.35). On the basis of a point score of one or two, the probability of severe AKI was 0.18 and 0.28 with an area under the curve of 0.71. CONCLUSION: This clinical prediction rule provides a novel and diagnostically accurate strategy for the potential prevention and improved management of kidney complications in patients with NE and, ultimately, for a possible decrease in unnecessary hospitalization in a high number of patients.

Evaluation of lipase levels in patients with nephropathia epidemica--no evidence for acute pancreatitis.

BACKGROUND: The most common causative agent for hemorrhagic fever with renal syndrome in Germany is Puumala virus (PUUV) and a high percentage of patients with PUUV infection have gastrointestinal (GI) symptoms. The aim of the present study was to determine the prevalence of increased lipase levels and acute pancreatitis during nephropathia epidemica (NE) in 166 patients from Germany. METHODS: Clinical and laboratory data during the acute phase of the disease were obtained from medical reports and files from 456 patients during acute hantavirus infection. Patients in whom serum lipase levels were determined during acute course of the disease were included in the study. RESULTS: Lipase levels at the time of diagnosis were determined in 166 of the 456 NE patients (36%). Of the 166 patients, 25 (15%) had elevated lipase levels at the time of admission to hospital or first contact with general practitioner/nephrologist. In total 7 patients had a threefold increased serum lipase above the normal range. Abdominal pain was not more often present in the group of patients with elevated serum lipase compared to the lipase-negative group (9/25 vs 58/141). Abdominal ultrasound and CT scans revealed no signs of pancreatitis in any of the patients. Patients with elevated serum lipase had higher serum creatinine peak levels (p = 0.03) during the course of the disease. CONCLUSIONS: Elevated lipase levels were common in our patient cohort and might reflect a more severe form of NE. NE does not lead to acute pancreatitis.

Determination of procalcitonin levels in patients with nephropathia epidemica - a useful tool or an unnecessary diagnostic procedure?

BACKGROUND/AIMS: Puumala virus causes nephropathia epidemica (NE), a milder form of hemorrhagic fever with renal syndrome that occurs in Central and Northern Europe. Several studies have sought to identify risk factors for severe NE. However, elevated procalcitonin (PCT) levels have not previously been investigated as a predictive marker for a severe course of NE. METHODS: A cross-sectional prospective survey of 456 adults with serologically confirmed NE was performed. RESULTS: PCT levels at the time of diagnosis were available for 43 out of 456 patients, and in 24 of these patients (56%) PCT levels were elevated ("PCT positive"). C-reactive protein (CRP) levels at admission to hospital and peak CRP levels during the acute course of the disease were higher in the PCT-positive compared with the PCT-negative group (p<0.05). Severe acute kidney injury (AKI) (RIFLE I and F) was present in similar numbers of PCT-positive and -negative patients (p=0.7), but antibiotics were more frequently used in the PCT-positive than the PCT-negative group (p<0.05). Within the PCT-positive group, PCT levels were similar among those receiving and not receiving antibiotics (p=0.13), and neither the duration of hospital stay nor CRP peak levels were lower in those treated with antibiotics (p=0.12 and p=0.13, respectively). CONCLUSIONS: Elevated PCT levels are common in patients with acute NE. There was no association between PCT levels and severity of disease, including AKI or thrombocytopenia. It is important to distinguish Puumala virus infection from other causes of AKI with thrombocytopenia. However, PCT might not be useful in differentiating hantavirus infection from bacterial infection.

Drug-induced acid-base disorders.

The incidence of acid-base disorders (ABDs) is high, especially in hospitalized patients. ABDs are often indicators for severe systemic disorders. In everyday clinical practice, analysis of ABDs must be performed in a standardized manner. Highly sensitive diagnostic tools to distinguish the various ABDs include the anion gap and the serum osmolar gap. Drug-induced ABDs can be classified into five different categories in terms of their pathophysiology: (1) metabolic acidosis caused by acid overload, which may occur through accumulation of acids by endogenous (e.g., lactic acidosis by biguanides, propofol-related syndrome) or exogenous (e.g., glycol-dependant drugs, such as diazepam or salicylates) mechanisms or by decreased renal acid excretion (e.g., distal renal tubular acidosis by amphotericin B, nonsteroidal anti-inflammatory drugs, vitamin D); (2) base loss: proximal renal tubular acidosis by drugs (e.g., ifosfamide, aminoglycosides, carbonic anhydrase inhibitors, antiretrovirals, oxaliplatin or cisplatin) in the context of Fanconi syndrome; (3) alkalosis resulting from acid and/or chloride loss by renal (e.g., diuretics, penicillins, aminoglycosides) or extrarenal (e.g., laxative drugs) mechanisms; (4) exogenous bicarbonate loads: milk-alkali syndrome, overshoot alkalosis after bicarbonate therapy or citrate administration; and (5) respiratory acidosis or alkalosis resulting from drug-induced depression of the respiratory center or neuromuscular impairment (e.g., anesthetics, sedatives) or hyperventilation (e.g., salicylates, epinephrine, nicotine).

Diagnostic impact of percutaneous renal biopsy.

BACKGROUND: Ultrasound-guided percutaneous renal biopsy (PRB) is an important diagnostic tool for nephrologists. Athough widely used and without question of pivotal importance for the diagnosis of renal diseases, little systematic data regarding standardized indications, outcomes, or consequences for this procedure are available. The aim of this study was to compare the clinically suspected diagnosis with the morphological results and the potential impact of PRB on the treatment of the patient. METHODS: 205 patients who underwent PRB of the native kidney within a 4-year period were included in this retrospective analysis. The biopsy results (BR), discharge diagnosis (DD), and the suspected diagnoses (SD) of the attending nephrologists prior to biopsy were documented. RESULTS: Mean age of the patients was 58 (range 44 - 77) years. The majority of patients (61%) received PRB during an acute disease phase, whereas 39% had elective PRB. Percutaneous biopsy of the native kidney led to a discharge diagnosis in 92% of the patients, with low complication rates (with 3 out of 205 patients had major bleeding complications). In ~ 2/3, the nephrologists were correct with the suspected diagnosis prior to the biopsy. In ~ 74% of the biopsies, a disease was identified that was potentially responsive to treatment modification. CONCLUSIONS: In summary, PRB was found to be a safe procedure that confirmed the suspected clinical diagnosis in two thirds of patients. As one third of the histopathological analyses demonstrated a non-suspected disease, the biopsies were of major importance for the correct treatment of the patients.

Polyuria in Hantavirus Infection Reflects Disease Severity and Is Associated with Prolonged Hospital Stay: A Systematic Analysis of 335 Patients from Southern Germany.

Background/Aims: Puumala virus (PUUV) infection leads to nephropathia epidemica (NE), especially in endemic areas in Central Europe. The clinical course of NE is characterized by acute kidney injury (AKI) with thrombocytopenia followed by polyuria to a different degree. The prevalence of polyuria and its associated risk factors have not been reported in a large cohort of NE patients. Methods: Clinical and laboratory data during the acute phase of the disease were obtained from the medical reports and files of 335 patients who received in-hospital treatment during acute hantavirus infection. Comprehensive statistical models were developed to estimate the probability of polyuria. Results: The median age at diagnosis was 47 years (interquartile range, IQR 40-59) and 48% of the patients developed polyuria with a urinary output of 5,100 ml/day (IQR 4,200-7,300). The hospital stay was significantly longer in the polyuric group compared to the nonpolyuric group [8 days (IQR 6-10) vs. 6 days (IQR 5-8); p = 0.04]. Using logistic regression analysis, male gender (odds ratio, OR = 1.6; 95% confidence interval, CI 1.05-2.58; p = 0.03), oliguria/anuria during NE (OR = 2.56; 95% CI 1.65-4.01; p < 0.001), severe AKI (OR = 1.87; 95% CI 1.22-2.9; p < 0.001), and hematuria (OR = 1.78; 95% CI 1.02-3.15; p = 0.04) were significantly associated with the development of polyuria. In a multivariate model, the probability of polyuria was 0.19 (SEM ± 0.05) in female patients presenting with mild/moderate AKI without anuria/oliguria. Conclusions: Almost 50% of hospitalized NE patients developed polyuria, which was associated with a prolonged hospital stay. The probability of the development of polyuria was lowest in female patients with mild/moderate, non-oliguric/anuric AKI. © 2014 S. Karger AG, Basel.

Platelet-derived growth factor receptor-ß expression in human peritoneum.

INTRODUCTION: Simple peritoneal fibrosis and encapsulating peritoneal sclerosis (EPS) are important lesions in the peritoneum of patients on peritoneal dialysis (PD). We have previously described a population of podoplanin-positive myofibroblasts in peritoneal biopsies from patients with EPS. Platelet-derived growth factor receptor-ß (PDGFRß) is a marker of pericytes, and PDGFs might be involved in the fibrotic response of the peritoneum. This study aimed to describe PDGFRß in the human peritoneum. METHODS: In this retrospective analysis, we localized PDGFRß in peritoneal biopsies from patients with EPS (n = 6) and patients on PD without signs of EPS (n = 5), and compared them with normal peritoneum (n = 4) and peritoneum from uremic patients (n = 5). Consecutive sections were stained for smooth-muscle actin (SMA) and podoplanin. Slides were scored semiquantitatively by 2 observers blinded to the diagnosis. RESULTS: PDGFRß was expressed by cells of arterial walls in all biopsies. A prominent population of PDGFRß-positive cells was present in the normal peritoneum, which were SMA negative on consecutive sections. In patients on PD, a high number of PDGFRß were also positive for SMA. In EPS, the majority of podoplanin-positive cells were positive for PDGFRß. In peritoneal biopsies from normal and uremic patients, the expression of SMA was mainly restricted to cells of arterial walls. Podoplanin expression was restricted to lymphatic vessels in normal peritoneum, in uremic patients, and in patients on PD without EPS. CONCLUSIONS: As podoplanin-positive myofibroblasts express PDGFRß, these cells might be related to pericytes (rather than other sources of fibroblasts). PDGFRß might turn out to be a therapeutic target in EPS.

Encapsulating peritoneal sclerosis: a rare, serious but potentially curable complication of peritoneal dialysis-experience of a referral centre in Germany.

BACKGROUND: Chronic peritoneal dialysis (PD) can be complicated by encapsulating peritoneal sclerosis (EPS), the most severe complication associated with long-term PD. METHODS: In this study, we retrospectively analysed 49 EPS patients regarding clinical presentation, histopathological findings, treatment and long-term clinical outcome at our referral centre. Patients were divided into two clinical categories: severe and mild/moderate. RESULTS: All patients in the severe group and most patients in the mild/moderate group had symptoms consistent with EPS. The most common computed tomographic findings were peritoneal thickening in both groups. Small bowel dilatation was frequently present in the severe group. The time of onset of symptoms consistent with EPS to the surgical procedure was median 5 months with an inter-quartile range of 2-12 months in the severe group. To date, 25 of 31 patients in the severe group (follow-up 45.6 ± 39.0 months after surgery) are alive. In the mild/moderate group, 8 of 11 patients are alive (follow-up 41.6 ± 21.6 months). The histological features were consistent with EPS in all biopsies. CONCLUSIONS: The outcome of patients even with severe EPS is not worse. It is a precondition that these patients are treated in specialized referral centres. The time of first clinical symptoms consistent with EPS to requirement of surgery is very short. Earlier diagnosis of the disease is mandatory, even in asymptomatic patients.

Analysis of α-klotho, fibroblast growth factor-, vitamin-D and calcium-sensing receptor in 70 patients with secondary hyperparathyroidism.

BACKGROUND/AIMS: Secondary hyperparathyroidism (sHPT) is known as a very common complication in patients with chronic kidney disease, and G-protein-coupled calcium-sensing receptor (CaSR), Vitamin D receptor (VDR) and Fibroblast growth factor receptor (FGFR)/Klotho complexes seem to be involved in its development. METHODS: Hyperplastic parathyroid glands from 70 sHPT patients and normal parathyroid tissue from 7 patients were obtained during parathyroidectomy. Conventional morphological and immunohistochemical analysis of parathyroid glands was performed after dividing each slide in a 3x3 array. RESULTS: The presence of lipocytes in the normal parathyroid gland and tissue architecture (nodal in patients with sHPT) allows for discrimination between normal parathyroid glands and parathyroid glands of patients with sHPT. Protein expression of Klotho, FGFR, CaSR and VDR was higher in the normal parathyroid glands compared to the sHPT group (p<0.001, p=0.07, p =0.01 and p=0.001). The variability of each protein expression within each tissue slide was high. Therefore correlations between the different immunohistochemical variables were analyzed for each of the nine fields and than analyzed for all patients. Using this analysis, a highly significant positive correlation could be found between the expression of FGFR and VDR (p=0.0004). Interestingly, in terms of VDR we found a shift to a more mixed nuclear/cytoplasmic staining in the HPT group compared to normal parathyroid gland cells, which showed solitary nuclear staining for VDR (p>0.05). CONCLUSIONS: CaSR, VDR and an impaired Klotho-FGFR-axis seem to be the major players in the development of sHPT. Whether the detected correlation between FGFR and VDR and the shift to a more mixed nuclear/cytoplasmic staining of VDR will yield new insights into the pathogenesis of the disease has to be evaluated in further studies.

Influence of thyroid function on different kidney function tests.

BACKGROUND/AIMS: The commonly used kidney function tests have limitations, especially in thyroid dysfunction. Therefore, we studied the most commonly used kidney function tests in patients with hypo- and hyperthyroidism and after reaching euthyroidism. METHODS: Prospective case series in 16 patients with thyroid dysfunction. Serum creatinine, 24-hour creatinine clearance, calculated glomerular filtration rate (GFR) by Cockroft-Gault, estimated GFR (eGFR) by the Chronic Kidney Disease Epidemiology Collaboration equation, serum cystatin C, eGFR based on cystatin C, eGFR based on a combined (cystatin C and creatinine) formula and plasma neutrophil gelatinase-associated lipocalin (NGAL) were measured in hypo- and hyperthyroidism and after gaining euthyroidism. RESULTS: When free thyroxine (fT(4)) normalized in hypothyroid patients, creatinine decreased and creatinine-based eGFR increased significantly. In contrast, cystatin C increased and eGFR based on cystatin C decreased significantly. There was no significant change in NGAL levels. When fT(4) normalized in patients with hyperthyroidism, creatinine increased and creatinine-based eGFR decreased significantly. In contrast, cystatin C decreased and cystatin-C-based GFR increased significantly. There was no significant change in NGAL levels. CONCLUSIONS: Thyroid function has a major influence on the vast majority of kidney function tests. Cystatin C is strongly influenced by the thyroid function and should be avoided in thyroid disorders. There was no effect on the plasma NGAL levels. The recommended kidney function test is a measurement of creatinine-based eGFR.

Tubulointerstitial nephritis in active tuberculosis - a single center experience.

BACKGROUND: Tuberculosis (TB) is a common disease worldwide, but kidney affection, i.e. tubulointerstitial nephritis (TIN) caused by Mycobacterium tuberculosis is rare. More frequent in patients with TB is drug induced TIN, i.e. the result of intensive antitubercular treatment. PATIENTS AND METHODS: In the time between April 2005 until August 2011 data from all patients (4 male, 1 female) with clinical evidence of active TB and significant renal disease were collected. All patients were treated with antitubercular treatment according to standard protocols. All patients underwent kidney biopsy due to progressive renal failure and all of the renal biopsies revealed an interstitial inflammation with eosinophilia. Epitheloid granulomata were found in 3 of 5 patients, whereas caseating granulomata were found in only one patient. No patient had sterile leucozyturia and all patients were negative for Mycobacterium tuberculosis on PCR; of note, none of the renal biopsies examined were positive for acid and alcohol fast bacilli by Ziehl-Neelsen staining. CONCLUSIONS: TB associated TIN is rare, but needs a rapid recognition and an early treatment. Kidney biopsy should be performed in patients with TB and renal disease to ensure the diagnosis of renal involvement of active TB and established correct treatment (intensifying TB treatment or changing TB therapy in drug induced TIN). Additionally, negative PCR of the histopathological samples should not exclude TB associated TIN and sterile leukocyturia is less common than expected.

Podoplanin-positive cells are a hallmark of encapsulating peritoneal sclerosis.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) and simple peritoneal sclerosis are important complications of long-term peritoneal dialysis (PD). Podoplanin is expressed by mesothelial cells and lymphatic vessels, which are involved in inflammatory reactions in the peritoneal cavity. METHODS: We studied 69 peritoneal biopsies from patients on PD (n = 16), patients with EPS (n = 18) and control biopsies taken at the time of hernia repair (n = 15) or appendectomy (n = 20). Immunohistochemistry was performed to localize podoplanin. Additionally, markers of endothelial cells, mesothelial cells, myofibroblasts (smooth muscle actin), proliferating cells, and double labelling for smooth muscle actin/podoplanin were used on selected biopsies. RESULTS: Podoplanin was present on the endothelium of lymphatic vessels in the submesothelial fibrous tissue and on mesothelial cells. In patients on PD and in biopsies with appendicitis, the mesothelial cells demonstrated a cuboidal appearance and circumferential podoplanin staining, with gaps between the cells. The number of lymphatic vessels was variable, but prominent at sites of fibrosis. In patients with EPS, a diffuse infiltration of podoplanin-positive cells with a fibroblastic appearance was present in 15 out of 18 biopsies. This pattern was focally present in 3 out of 16 on PD and none in the 35 controls. The podoplanin-positive cells did not express the endothelial marker or the mesothelial marker (calretinin). CONCLUSIONS: EPS is characterized by a population of podoplanin and smooth muscle actin double-positive cells. Podoplanin might be a suitable morphological marker supporting the diagnosis and might be involved in the pathogenesis of EPS.

Characterization and outcome following Puumala virus infection: a retrospective analysis of 75 cases.

BACKGROUND: Infection with the Puumala virus (PUUV), which belongs to the Hantavirus family, is a common but often neglected cause of acute kidney injury (AKI) in endemic areas of Europe. The objective of the present study was to systematically analyse clinical presentation and renal outcomes following PUUV infection. METHODS: In a retrospective study, we analysed data from 75 patients who were admitted to two large hospitals in Germany over an 8-year period and who tested positive for PUUV infection. Clinical and laboratory data were collected from patient files; creatinine levels before admission and during follow-up were obtained from phone calls. RESULTS: Patients were between 16 and 82 years old (average +/- SD, 40.4 +/- 13.4) with a male to female ratio of 2.5:1. They showed a wide variety of clinical presentations with renal failure being the cause of admission in only 50%. AKI developed in 95% of patients who showed maximum creatinine levels of 4.3 +/- 0.3 mg/dl. Four patients required temporary dialysis, and one patient died from pulmonary complications. Thrombocytopaenia (137 +/- 11 x 10(3)/microl) was present in almost all cases, and elevated levels of lactate dehydrogenase (LDH) and C-reactive protein (CRP) were observed in 57 and 100% of patients, respectively. Urinalysis revealed mild to nephrotic proteinuria in 85%, which was often associated with haemoglobinuria. All patients showed full recovery of renal function and return to pre-existing normal serum creatinine levels. CONCLUSION: In a majority of cases, PUUV infection results in thrombocytopenic AKI. Fever is a requirement for diagnosis, while elevated LDH and CRP values are also frequently observed. Overall, early renal outcomes were excellent.