Focal segmental glomerulosclerosis in a patient with multiple sclerosis treated with Teriflunomide and Ocrelizumab.

We describe the case of a 24-year-old male patient with multiple sclerosis (MS) who was treated with Teriflunomide for eight months. However, due to MS progression, treatment was switched to Ocrelizumab. After 15 months of therapy with Ocrelizumab the patient developed edema and nephrotic-range albuminuria. Kidney biopsy showed focal segmental glomerulosclerosis (FSGS) and Ocrelizumab treatment was stopped. Teriflunomide is less likely to have caused FSGS due to a three week wash-out period and a timespan of 15 months between the last Teriflunomide dose and development of albuminuria. Treatment with Ocrelizumab has been associated with organ-specific inflammation in MS-patients, thus an association between the development of FSGS and Ocrelizumab therapy is possible, and this case suggests considering this potential association.

First-year mortality in incident dialysis patients: results of the Peridialysis study.

BACKGROUND: Controversy surrounds which factors are important for predicting early mortality after dialysis initiation (DI). We investigated associations of predialysis course and circumstances affecting planning and execution of DI with mortality following DI. METHODS: Among 1580 patients participating in the Peridialysis study, a study of causes and timing of DI, we registered features of predialysis course, clinical and biochemical data at DI, incidence of unplanned suboptimal DI, contraindications to peritoneal dialysis (PD) or hemodialysis (HD), and modality preference, actual choice, and cause of modality choice. Patients were followed for 12 months or until transplantation. A flexible parametric model was used to identify independent factors associated with all-cause mortality. RESULTS: First-year mortality was 19.33%. Independent factors predicting death were high age, comorbidity, clinical contraindications to PD or HD, suboptimal DI, high eGFR, low serum albumin, hyperphosphatemia, high C-reactive protein, signs of overhydration and cerebral symptoms at DI. Among 1061 (67.2%) patients who could select dialysis modality based on personal choice, 654 (61.6%) chose PD, 368 (34.7%) center HD and 39 (3.7%) home HD. The 12-months survival did not differ significantly between patients receiving PD and in-center HD. CONCLUSIONS: First-year mortality in incident dialysis patients was in addition to high age and comorbidity, associated with clinical contraindications to PD or HD, clinical symptoms, hyperphosphatemia, inflammation, and suboptimal DI. In patients with a "free" choice of dialysis modality based on their personal preferences, PD and in-center HD led to broadly similar short-term outcomes.

Peritoneal dialysis resulting in discontinuance of recurring attacks of acute intermittent porphyria: A case report.

Acute intermittent porphyria is one of eight disorders arising from disturbances in heme biosynthesis where the precursors, 5-aminolevulinate and porphobilinogen, are elevated in plasma and urine. Attacks are characterized by severe abdominal pain, vomiting and/or obstipation, neurological manifestations, and psychological disturbances. The mainstay of treatment is hemin infusion to induce the negative feedback of heme synthesis. Hemodialysis is casuistically suggested as an alternative treatment. We present a case report of a 78-year-old male with acute intermittent porphyria and renal failure treated with peritoneal dialysis resulting in complete discontinuance of longstanding painful and disabling porphyria attacks.

Choice of dialysis modality among patients initiating dialysis: results of the Peridialysis study.

BACKGROUND: In patients with end-stage kidney disease (ESKD), home dialysis offers socio-economic and health benefits compared with in-centre dialysis but is generally underutilized. We hypothesized that the pre-dialysis course and institutional factors affect the choice of dialysis modality after dialysis initiation (DI). METHODS: The Peridialysis study is a multinational, multicentre prospective observational study assessing the causes and timing of DI and consequences of suboptimal DI. Clinical and biochemical data, details of the pre-dialytic course, reasons for DI and causes of the choice of dialysis modality were registered. RESULTS: Among 1587 included patients, 516 (32.5%) were judged unsuitable for home dialysis due to contraindications [384 ( 24.2%)] or no assessment [106 (6.7%); mainly due to late referral and/or suboptimal DI] or death [26 (1.6%)]. Older age, comorbidity, late referral, suboptimal DI, acute illness and rapid loss of renal function associated with unsuitability. Of the remaining 1071 patients, 700 (65.4%) chose peritoneal dialysis (61.7%) or home haemodialysis (HD; 3.6%), while 371 (34.6%) chose in-centre HD. Somatic differences between patients choosing home dialysis and in-centre dialysis were minor; factors linked to the choice of in-centre dialysis were late referral, suboptimal DI, acute illness and absence of a 'home dialysis first' institutional policy. CONCLUSIONS: Given a personal choice with shared decision making, 65.4% of ESKD patients choose home dialysis. Our data indicate that the incidence of home dialysis potentially could be further increased to reduce the incidence of late referral and unplanned DI and, in acutely ill patients, by implementing an educational programme after improvement of their clinical condition.

[Cannabinoid hyperemesis syndromecan be relieved by hot showers].

This is a case report of a 19-year-old woman with cannabinoid hyperemesis syndrome (CHS), which is characterised by cyclic vomiting and nausea, relieved by hot showers and caused by chronic cannabis usage. Many diagnoses must be ruled out, but the suspicion of cannabis usage must be present. Early suspicion of CHS can prevent overtreatment and unnecessary investigations. Lack of evidence makes treatment difficult and is primarily symptomatic. Attention to cannabis usage is needed when admitting patients with emesis.

Suboptimal dialysis initiation is associated with comorbidities and uraemia progression rate but not with estimated glomerular filtration rate.

BACKGROUND: Despite early referral of uraemic patients to nephrological care, suboptimal dialysis initiation (SDI) remains a common problem associated with increased morbimortality. We hypothesized that SDI is related to pre-dialysis care. METHODS: In the 'Peridialysis' study, time and reasons for dialysis initiation (DI), clinical and biochemical data and centre characteristics were registered during the pre- and peri-dialytic period for 1583 end-stage kidney disease patients starting dialysis over a 3-year period at 15 nephrology departments in the Nordic and Baltic countries to identify factors associated with SDI. RESULTS: SDI occurred in 42%. Risk factors for SDI were late referral, cachexia, comorbidity (particularly cardiovascular), hypoalbuminaemia and rapid uraemia progression. Patients with polycystic renal disease had a lower incidence of SDI. High urea and C-reactive protein levels, acidosis and other electrolyte disorders were markers of SDI, independently of estimated glomerular filtration rate (eGFR). SDI patients had higher eGFR than non-SDI patients during the pre-dialysis period, but lower eGFR at DI. eGFR as such did not predict SDI. Patients with comorbidities had higher eGFR at DI. Centre practice and policy did not associate with the incidence of SDI. CONCLUSIONS: SDI occurred in 42% of all DIs. SDI was associated with hypoalbuminaemia, comorbidity and rate of eGFR loss, but not with the degree of renal failure as assessed by eGFR.

[Outbreak of nephropathiaepidemica in Jutland, Denmark].

In Denmark, most cases of nephropathia epidemica (NE) occur on the island of Funen and are caused by the transmission of Puumala hantavirus to humans from the bank vole. This is a case report comprising four cases of NE occurring in close vicinity to Silkeborg, Jutland, where the disease is not usually seen. NE is characterised by increased vascular permeability, and patients present with flu-like symptoms progressing to acute kidney injury. When NE occurs in areas where it has not traditionally been endemic, awareness of the disease is important to ensure proper diagnosis.

Challenges in the measurement of plasma creatinine on the Roche cobas c702.

The aim of this study was to document the differences between two Roche creatinine measurement methods, the CREP2 test on the cobas c702 and the CREA PLUS test on the Modular P. Samples with creatinine isotope dilution mass spectrometry (IDMS) values were analyzed on both instruments. Method comparison using the remaining plasma samples was performed twice, using two different lot numbers of reagents and two different lot numbers of calibrators on both instruments. Medians and percentiles of the plasma creatinine values produced on the Modular P and cobas c702 from 2012 to 2017 were compared. The recovery of samples with IDMS creatinine values (SRM 967a level 1, SRM 967a level 2, serum X and five serum pools from Roche) was 101.7%-110.2% on the cobas c702 and 98.9%-102.6% on the Modular P. Comparison of the two methods showed that the slope was close to 1.0 using linear, Deming and Passing Bablok regressions, but all equations showed a negative intercept, indicating that the cobas c702 overestimates plasma creatinine in relation to the Modular P by 4-6 µmol/L. The median value for routine plasma creatinine lies between 74 and 77 µmol/L for the Modular P and 81 µmol/L for the cobas c702. After the cobas c702 was factorized in September 2016, the median plasma creatinine value decreased to 75 µmol/L. In conclusion, the CREP2 method on the cobas c702 overestimates creatinine by 4-6 µmol/L, which has a significant influence on the estimated glomerular filtration rate (eGFR) in children.

Two brothers with identical variants of the CLCN5 gene-one developing Dent's disease.

Dent's disease is characterized by manifestations of proximal tubule dysfunction including hypercalciuria, kidney stones, proteinuria, rickets and progressively declining kidney function. The diagnosis is based on the presence of low-molecular-weight proteinuria, hypercalciuria and at least one of the following: nephrocalcinosis, kidney stones, haematuria, hypophosphataemia or renal insufficiency. Dent's disease is a hereditary condition that is caused by variants in the CLCN5 gene or the OCRL1 gene and affects only males. Herein, we report on two brothers who were found to have a previously reported disease-causing variant in the CLCN5 gene. One sibling had nephrocalcinosis, proteinuria and hypercalciuria, whereas the other sibling was asymptomatic and had normal laboratory findings.

Reference intervals for plasma cystatin C and plasma creatinine in adults using methods traceable to international calibrators and reference methods.

INTRODUCTION: The aim of this study was to establish reference intervals for plasma cystatin C and creatinine in adults using the Gentians cystatin C method traceable to the international calibrator standard ERM-DA471/IFCC and a creatinine method traceable to the IDMS (Isotope Dilution Mass Spectrometry) creatinine reference method. METHODS: Blood samples were collected from 304 healthy blood donors (152 men and 152 women between 17 and 66 years old) with 30-31 men and 30-31 women in each ten-year interval. Plasma cystatin C was analyzed using the Gentian Cystatin C assay on a Roche cobas c702 analyzer, and plasma creatinine was analyzed using the CREA Plus assay on the Roche Modular P analyzer. RESULTS: The nonparametric reference intervals for plasma cystatin C were 0.58-1.00 mg/L in women (median 0.78 mg/L, range 0.56-1.06 mg/L) and 0.62-1.04 mg/L in men (median 0.79 mg/L, range 0.61-1.07 mg/L). The Mann-Whitney U test revealed no gender-related difference in plasma cystatin C (P = .21). A common reference interval in women and men was calculated to be 0.61-1.01 mg/L (median 0.79 mg/L, range 0.56-1.07 mg/L). The nonparametric reference interval for plasma creatinine was 52-89 µmol/L in women (median 69 µmol/L, range 52-92 µmol/L) and 61-108 µmol/L in men (median 86 µmol/L, range 56-118 µmol/L). The Mann-Whitney U test revealed a gender-related difference in plasma creatinine (P < .0001). CONCLUSION: In conclusion, we have established reference intervals for plasma cystatin C and creatinine in adults using methods traceable to international standards.

Postprandial Mineral Handling in Patients on Maintenance Hemodialysis.

OBJECTIVE: Patients on maintenance hemodialysis (HD) are unable to compensate for an enlarged mineral load with increased excretion of calcium and phosphate in the urine. Hence, excess calcium and phosphate must be neutralized by other mechanisms to avoid toxicity. The present study examined the acute handling of a mineral load in HD patients as compared with healthy subjects. DESIGN: Controlled intervention study. SUBJECTS: Twelve HD patients and 12 matched healthy subjects. INTERVENTION: After a weight-adjusted standardized meal, blood samples were collected for the following 9 hours for ionized calcium, phosphate, parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF23). The fractional excretion of calcium and phosphate was measured in controls. The patients were not allowed to take phosphate binders 24 hours before the experiment, and the study was performed on a non-HD day. RESULTS: In healthy subjects, plasma calcium and phosphate did not change significantly from baseline, whereas HD patients demonstrated a decrease in plasma phosphate from 60 to 120 minutes by maximum 10% ([6; 13%], mean [95% confidence interval], P < .001) below baseline. PTH increased in both HD patients and controls and peaked 300 minutes after the meal 11% ([4; 19%], P < .004) above baseline in both groups. No changes in FGF23 were observed in HD patients, whereas FGF23 steadily decreased in controls, reaching nadir values at the end of the study 16% ([10; 21%], P < .001) below baseline. Control subjects demonstrated an immediate postprandial increase in the fractional excretion of both calcium and phosphate CONCLUSIONS: In HD patients, the mineral load paradoxically induced a decrease in plasma phosphate, whereas ionized calcium remained unchanged although PTH increased. These findings suggest that excess calcium and phosphate may be disposed of by mineral deposition, which may include soft tissue and vascular calcification.

Why do physicians prescribe dialysis? A prospective questionnaire study.

INTRODUCTION: The incidence of unplanned dialysis initiation (DI) with consequent increased comorbidity, mortality and reduced modality choice remains high, but the optimal timing of dialysis initiation (DI) remains controversial, and there is a lack of studies of specific reasons for DI. We investigated why and when physicians prescribe dialysis and hypothesized that physician motivation for DI is an independent factor which may have clinical consequences. METHODS: In the Peridialysis study, an ongoing multicenter prospective study assessing the causes and timing of DI and consequences of unplanned dialysis, physicians in 11 hospitals were asked to describe their primary, secondary and further reasons for prescribing DI. The stated reasons for DI were analyzed in relation to clinical and biochemical data at DI, and characteristics of physicians. RESULTS: In 446 patients (median age 67 years; 38% females; diabetes 25.6%), DI was prescribed by 84 doctors who stated 23 different primary reasons for DI. The primary indication was clinical in 63% and biochemical in 37%; 23% started for life-threatening conditions. Reduced renal function accounted for only 19% of primary reasons for DI but was a primary or contributing reason in 69%. The eGFR at DI was 7.2 ±3.4 ml/min/1.73 m2, but varied according to comorbidity and cause of DI. Patients with cachexia, anorexia and pulmonary stasis (34% with heart failure) had the highest eGFR (8.2-9.8 ml/min/1.73 m2), and those with edema, "low GFR", and acidosis, the lowest (4.6-6.1 ml/min/1.73 m2). Patients with multiple comorbidity including diabetes started at a high eGFR (8.7 ml/min/1.73 m2). Physician experience played a role in dialysis prescription. Non-specialists were more likely to prescribe dialysis for life-threatening conditions, while older and more experienced physicians were more likely to start dialysis for clinical reasons, and at a lower eGFR. Female doctors started dialysis at a higher eGFR than males (8.0 vs. 7.1 ml/min/1.73 m2). CONCLUSIONS: DI was prescribed mainly based on clinical reasons in accordance with current recommendations while low renal function accounted for only 19% of primary reasons for DI. There are considerable differences in physicians´ stated motivations for DI, related to their age, clinical experience and interpretation of biochemical variables. These differences may be an independent factor in the clinical treatment of patients, with consequences for the risk of unplanned DI.

Response of fibroblast growth factor 21 to meal intake and insulin infusion in patients on maintenance haemodialysis.

OBJECTIVE: To investigate the response of serum fibroblast growth factor 21 (FGF21) to a meal and to insulin infusion in haemodialysis (HD) patients. DESIGN AND PATIENTS: Meal study: in a crossover design, 12 nondiabetic HD patients were randomly assigned to: (1) a non-HD day with one meal served, (2) a HD day with one meal served during HD and (3) a HD day with two meals served during and after HD, respectively. Twelve healthy controls participated in an experiment identical to the non-HD day. Insulin infusion study: in a crossover design, 11 nondiabetic HD patients were randomly assigned to receive a 4-h HD session with either: (1) no infusion, (2) glucose infusion or (3) glucose-insulin infusion. A meal was served 2 h before HD start. RESULTS: Meal study: serum FGF21 was 23-fold higher in HD patients than controls (P < 0·001). Postprandial FGF21 decreased on all four study days (P < 0·006), but the relative reductions from baseline were significantly greater in controls (P < 0·008). Postprandial changes in FGF21 were inversely related with triglycerides (P = 0·042) and positively related with insulin-like growth factor binding protein-1 (IGFBP-1) (P < 0·001). Serum FGF21 was only associated with changes in adiponectin (P = 0·001) and free fatty acids (P = 0·04) in the healthy controls. Insulin infusion study: as compared with no infusion, glucose and glucose-insulin infusion prevented the postprandial decrease in FGF21 and resulted in higher FGF21 concentrations by up to 25% (P = 0·003). CONCLUSIONS: Serum FGF21 was highly elevated in HD patients but the response of serum FGF21 to meal intake and insulin infusion seemed to be intact. Our results indicate that FGF21 may play an important role in short-term metabolic homoeostasis.

Impaired postprandial response of the insulin-like growth factor system in maintenance haemodialysis.

OBJECTIVE: Patients on maintenance haemodialysis (HD) have reduced circulating free and bioactive insulin-like growth factor I (IGF-I) due to increased IGF-binding proteins (IGFBPs). This study investigated the postprandial response of the IGF system in HD patients compared with matched healthy subjects. DESIGN AND PATIENTS: In a crossover study, twelve nondiabetic HD patients were assigned in a random order to three 10-h study days: (1) a non-HD day with one meal served at baseline (NHDM1), (2) an HD day with one meal served during HD (HDM1) and (3) an HD day with two meals served during and after HD, respectively (HDM2). Twelve healthy controls conducted session 1. RESULTS: After the baseline meal, insulin concentrations changed similarly in HD patients and controls, whereas hyperglycaemia was more prolonged in HD patients (P < 0·001). Postprandial IGFBP-1 showed greater reductions from baseline in controls (-76% [-81; -70%], mean [95% confidence intervals], P < 0·001) than in patients on non-HD days (-45% [-57; -30%], P < 0·001). In the latter group, the response was even more attenuated during HD (-22% [-38; -1%] and -24% [-40; -4%], P ≤ 0·041). After the second meal on HDM2 days, IGFBP-1 further decreased (-50% [-61; -37%], P < 0·001), whereas IGFBP-1 returned to baseline levels on the other study days. Consistently, at the end of the study days, bioactive IGF-I was significantly above baseline only on HDM2 days (+22% [+5; +43%], P = 0·012). CONCLUSIONS: HD patients were unable to suppress IGFBP-1 to the same extent as healthy controls, which may increase the risk of protein-energy wasting in maintenance HD. A second meal after HD, however, effectively suppressed IGFBP-1 and increased bioactive IGF-I.

Bilateral renal artery stenosis in a patient with chronic myeloid leukemia treated with nilotinib.

Previously authors have recently described an association between nilotinib therapy for chronic myeloid leukemia (CML) and severe peripheral artery disease, coronary artery disease and sudden death. We present a case report of a male patient with CML who received nilotinib therapy. He developed bilateral renal artery stenosis and renovascular hypertension. He had no history of hypertension, cardiovascular disease, or diabetes, and he was a nonsmoker. Together, these observations indicated that obtaining further understanding of the effects is necessary and that extreme caution is warranted when considering second-generation tyrosine kinase inhibitors for first-line therapy in CML.

Performance evaluation of the Roche Tina-quant Cystatin C assay and reference interval for cystatin C in healthy blood donors.

OBJECTIVE: To evaluate the performance of the Roche Diagnostics Tina-quant Cystatin C particle enhanced immuno turbidimetric assay for the measurement of plasma and serum cystatin C, and to establish reference intervals for cystatin C in healthy blood donors. METHODS AND MATERIALS: The cystatin C measurements were performed on the Roche Modular Analytics P automated clinical chemistry analyzer. RESULTS: The cystatin C assay was linear in the measuring range 0.40-7.00 mg/L. Within-run CVs < or = 2.0%, between-run CVs < or = 4.2%, and total CVs < or = 5.5% in plasma pools and in commercial cystatin C control materials (range 1.0-4.7 mg/L). Recovery was 99.4-109.3%. No interference was detected from haemoglobin < 0.9 mmol/L, bilirubin < 330 micromol/L and Intralipid < 20 g/L. Measurement of cystatin C in Li-heparin plasma did not differ significantly from cystatin C measured in serum. Forty patient samples run on the Modular Analytics P (y) were compared to the Siemens Cystatin C assay on the BN II (x): y = 0.817x + 0.270, Sy.x = 0.168 (Deming regression). The non-parametric reference interval for cystatin C was calculated to be 0.41-0.91 mg/L in females (n = 86), and 0.43-0.94 mg/L in males (n = 76). The Mann-Whitney U test showed a significant difference between the two genders (p = 0.015), but the difference was without clinical relevance. A common reference interval for both genders (n = 162) was calculated to be 0.41-0.92 mg/L. CONCLUSION: The performance of the Tina-quant Cystatin C assay was acceptable for clinical use.

Biological variation of cystatin C and creatinine.

OBJECTIVE: To evaluate the day-to-day biological variation of cystatin C in comparison with creatinine in healthy subjects and in patients with impaired renal function. MATERIAL AND METHODS: Eight weekly morning blood samples were taken from 20 healthy subjects (13 females and 7 males, median age 44 years, range 25-61) and 19 patients with impaired renal function (8 females and 11 males, median age 61 years, range 35-70). Serum cystatin C was measured using Dade Behring N Latex Cystatin C assay and serum creatinine by an enzymatic method (Roche). RESULTS: In the healthy subjects mean serum cystatin C was 0.70 mg/L (range 0.44-1.09) and mean serum creatinine 77 micromol/L (range 54-100). The analytical variance was 2.0% for cystatin C and 1.6% for creatinine. The intra-individual variance was greater for cystatin C than for creatinine (8.6% vs. 4.7%). The inter-individual variance was similar for both analytes (cystatin C 15.1% vs. creatinine 14.4%). In the patients with impaired renal function mean serum cystatin C was 1.86 mg/L (range 0.45-3.31) and mean serum creatinine 224 micromol/L (range 103-430). The analytical variance was 1.8% for cystatin C and 1.4% for creatinine. The intra-individual variance was greater for cystatin C than for creatinine (16.0% vs. 8.9%). CONCLUSION: In the present study, the intra-individual variance was greater for cystatin C than for creatinine in both healthy subjects and in patients with impaired renal function. Accordingly, serum creatinine is the preferred marker for serial monitoring of renal function in individuals with stable muscle mass.