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In this article, we present two cases of patients with acute renal insufficiency with a history of exocrine pancreatic insufficiency. In one case, this was caused by pancreaticoduodenectomy; in the other, by alcohol abuse. Neither patient had considerable proteinuria or haematuria. Their renal biopsies showed tubulopathy with widespread oxalate crystals, characterised by their birefringence in light microscopy. Restricting oxalate intake and prescribing oxalate binding agents reduced serum oxalate levels. Renal function partially recovered in both patients. Oxalate nephropathy is associated with exocrine pancreatic insufficiency, gastric and pancreatic surgery, and inflammatory bowel disease. Normally, dietary calcium binds oxalate to form calcium oxalate, which is excreted in the stool. In patients with pancreatic insufficiency, fatty acids bind calcium instead, allowing oxalate to be absorbed in the colon. The resulting hyperoxaluria can cause oxalate crystal formation, tubulopathy, and renal insufficiency. Treatment relies on decreasing the amount of absorbable oxalate in the intestinal lumen, as well as lowering urinary oxalate concentrations.Secondary hyperoxaluria is a common cause of renal insufficiency and should be considered in patients with a medical history of pancreatic insufficiency and progressive kidney injury.

Lithium is the most effective drug for mood stabilization in bipolar disorder. However, lithium exposure has been associated with an impaired renal concentrating ability (RCA) and glomerular filtration rate (GFR). We examined RCA and estimated GFR in a cohort of patients treated with lithium.134 patients (≥ 18 years of age) with a mood disorder treated with lithium were screened; 100 patients were included. Demographic and clinical characteristics and blood and urine samples were collected. Additionally, a dDAVP-test was performed to determine maximal RCA.A dDAVP-test was performed in 98 patients (37 males, 61 females). Mean age was 51 years (SD: 12), median duration of lithium therapy 7 years (IQR: 4-15), mean maximal urine osmolality (Uosmol) 725 mOsmol/kg (SD: 153), and median eGFR 84 ml/min/1.73 m2 (IQR: 68-95). Fifty patients (51%) had an impaired RCA and 17 patients (17%) had nephrogenic diabetes insipidus (Uosmol 600-800 and600 mOsmol/kg, respectively). Notably, clinical symptoms did not predict an impaired RCA. Nineteen patients (19%) had an eGFR ≤ 60 ml/min/ 1.73 m2. Multivariable regression analysis showed a significant association between the duration of lithium treatment and maximal Uosmol (B = -6.1, 95%-CI: -9.4, -2.9, p0.001) and eGFR (B = -0.6, 95%-CI: 0.2, -3.3; p0.01).RCA is impaired in the majority of lithium-treated patients. Both RCA and eGFR are inversely associated with the duration of lithium therapy. Prospective follow-up will enable us to evaluate if abnormalities in RCA can be used to predict the development of lithium-induced chronic kidney disease.

Dysregulation of complement activation is the most common cause of the atypical haemolytic uraemic syndrome (aHUS). Many patients with aHUS develop end-stage renal disease and consider kidney transplantation. However, the recurrence rate after transplantation ranges from 45-90% in patients with known abnormalities in circulating complement proteins. It was recently proposed that patients with aHUS should be treated prophylactically with plasma exchange or eculizumab to prevent recurrence after transplantation.A case series describing the successful outcome of kidney transplantation without prophylactic therapy in four adult patients with aHUS and a high risk of disease recurrence. Patients received a living donor kidney and immunosuppression consisting of basiliximab induction, low-dose tacrolimus, prednisone and mycophenolate mofetil. Patients received a statin, and were targeted to a low blood pressure preferably using blockers of the renin-angiotensin system.After a follow-up of 16-21 months, none of the patients developed recurrent aHUS. Also, no rejection was observed.Kidney transplantation in adult patients with aHUS can be successful without prophylactic eculizumab, using a protocol that minimises cold ischaemia time, reduces the risk of rejection and provides endothelial protection. Our data suggest that in patients with aHUS, controlled trials are needed to demonstrate the optimal strategy.

1 The pharmacokinetic and pharmacodynamic properties of the angiotensin converting enzyme (ACE) inhibitor cilazapril were studied in 30 hypertensive patients with various degrees of renal function. 2 After a single oral dose, apparent cilazaprilat clearance was dependent on renal function being 16.0±3.0, 11.1 ± 3.0, 8.7 ± 3.7 and 6.7 ± 2.1 l h-1 (means ± s.d.) in patients with creatinine clearances (CLcr) of > 100, 41-100, 21-40, and 8-20 ml min-1, respectively. 3 During 11 weeks of treatment with cilazapril, doses were adjusted to the CLcr and varied from 0.5 to 5.0 mg once daily. At 24 h after drug administration a clear antihypertensive response was seen only in the low clearance groups (CLcr < 40ml min-1). In contrast, and despite higher once daily dosages, the decline of mean arterial pressure was small and cilazaprilat concentrations after 24 h were lower in the high clearance groups. 4 This study demonstrates that chronic once daily treatment with cilazapril is effective in patients with impaired renal function at dosages adjusted to creatinine clearance. No accumulation was seen. Since cilazaprilat clearance was high in the high creatinine clearance groups, a clear antihypertensive response in these groups was only seen at 3 h after drug administration.

Chronic kidney disease (CKD) is associated with increased cardiovascular risk. Here we evaluate whether strict implementation of guidelines aimed at multiple targets with the aid of nurse practitioners (NP) improves management in patients with CKD.MASTER PLAN is a randomised controlled clinical trial, performed in nine Dutch hospitals. Patients with CKD (estimated glomerular filtration rate (eGFR) 20-70 ml÷min) were randomised to receive NP support (intervention group (IG)) or physician care (control group (CG)). Patients were followed for a median of five years. Presented data are an interim analysis on risk factor control at two-year follow-up.We included 788 patients (532 M, 256 F), (393 CG, 395 IG), mean (±SD ) age 59 (±13) years, eGFR 38 (±15) ml÷min÷1.73m(2), blood pressure (BP) 138 (±21)÷80 (±11) mmHg. At two years 698 patients (352 IG, 346 CG) could be analysed. IG as compared with CG had lower systolic (133 vs 135 mmHgsemi; p= 0.04) and diastolic BP (77 vs 80 mmHgsemi; p=0.007), LDL cholesterol (2.30 vs 2.45 mmol(-l); p= 0.03), and increased use of ACE inhibitors, statins, aspirin and vitamin D. The intervention had no effect on smoking cessation, body weight, physical activity or sodium excretion.In both groups, risk factor management improved. However, changes in BP control, lipid management and medication use were more pronounced in IG than in CG. Lifestyle interventions were not effective. Coaching by NPs thus benefits everyday care of CKD patients. Whether these changes translate into improvement in clinical endpoints remains to be established.

Blood pressure (BP) is the most important modifiable risk factor for cardiovascular (CV) disease and progression of kidney dysfunction in patients with chronic kidney disease. Despite extensive antihypertensive treatment possibilities, adequate control is notoriously hard to achieve. Several determinants have been identified which affect BP control. In the current analysis we evaluated differences in achieved BP and achievement of the BP goal between hospitals and explored possible explanations.At baseline, BP was measured in a supine position with an oscillometric device in 788 patients participating in the MASTER PLAN study. We also retrieved the last measured office BP from the patient records. Additional baseline characteristics were derived from the study database. Univariate and multivariate analyses were performed with general linear modelling using hospital as a random factor.In univariate analysis, hospital was a determinant of the level of systolic and diastolic BP at baseline. Adjustment for patient, kidney disease, treatment or hospital characteristics affected the relation. Yet, in a fully adjusted model, differences between centres persisted with a range of 15 mmHg for systolic BP and 11 mmHg for diastolic BP.Despite extensive adjustments, a clinically relevant, statistically significant difference between hospitals was found in standardised BP measurements at baseline of a randomised controlled study. We hypothesise that differences in the approach towards BP control exist at the physician level and that these explain the differences between hospitals.

Immunoglobulin A nephropathy (IgAN) is characterised by high variability in clinical course and outcome. Accurate prediction of prognosis is needed to optimise treatment. Urinary alpha1-microglobulin and beta2-microglobulin are markers of tubulointerstitial injury and predict the risk of end-stage renal disease (ESRD) in idiopathic membranous nephropathy. We questioned the relevance of these markers in IgAN.We included patients with biopsy proven IgAN, who were evaluated for proteinuria in our centre between 1995 and 2007. Data were analysed using univariate and multivariate Cox regression for the outcome variables ESRD and progression (rise in serum creatinine of50% or start of immunosuppressive therapy).Seventy patients (71% men) were selected. Median age was 39 years, median serum creatinine 140 micromol/l, and median proteinuria 2.4 g/day. Median urinary alpha1-microglobulin excretion was 23.5 microg/min (range 3.5-275.3) and median urinary beta2-microglobulin excretion was 0.4 microg/min (range 0.1-62.1). Both alpha1m and beta2m correlated significantly with serum creatinine (r = 0.65, p0.01 and r = 0.62, p0.01) and total proteinuria (r = 0.35, p0.01 and r = 0.28, p0.05). During follow-up (median 75 months) 25 patients (36%) developed ESRD , and 46 patients (66%) showed progression. 19 patients (27%) were treated with immunosuppressive agents. In univariate analysis urinary alpha1- and beta2-microglobulin predicted ESRD and progression. In multivariate analysis only serum creatinine and urinary protein were independent predictors of both outcomes.Urinary excretion of low molecular weight proteins did not offer an advantage over total proteinuria and serum creatinine in predicting prognosis in patients with IgAN.

Mean arterial pressure (MAP) is often used as an index of overall blood pressure. In recent years, the use of automated oscillometric blood pressure measurement devices is increasing. These devices directly measure and display MAP; however, MAP is often calculated from systolic blood pressure (SBP) and diastolic blood pressure (DBP) as displayed by the device. In this study we have analysed measured and calculated MAP, obtained by two different oscillometric BP measurement devices in two different patient cohorts. The first cohort included 242 healthy subjects (male 40.5%, 50+/-13 years). BP measurements were performed with a Welch Allyn 5300P device. We found a small but significant difference between measured MAP and calculated MAP (MAP(m-c:) -1.8 mmHg, range -5.7 to 12.9 mmHg, p0.001). MAP(m-c) showed a significant, but weak correlation with DBP and SBP. The second cohort included included 134 patients with glomerular diseases (male 63%, 50+/14 years). BP measurements were performed with a Dinamap 487210 device. In this group we also observed a small difference between measured MAP and calculated MAP (+1.7 mmHg, range -15.3 to 28.2 mmHg, p0.001). MAP (m-c) correlated with age, all blood pressure indices and heart rate. An overall analysis showed that age, SBP, DBP, and type of device are all independently related to MAP (m-c). There is a significant difference between measured and calculated MAP. The difference is small on average; however, this MAP(m-c) can be large in the individual patient. Moreover, there are differences of reported MAP between devices. Our data suggest that calculated and measured MAP cannot be used interchangeably.

Patients with proteinuria may suffer from substantial losses of functional proteins such as hormones and hormone-binding proteins. A limited number of studies have reported urinary losses of thyroid hormones and thyroxin-binding globulin. Overt hypothyroidism attributable to these urinary losses has been described. However, the impact of proteinuria on thyroid function parameters has not been studied in a large patient cohort.We evaluated thyroid function parameters in patients with proteinurea who are negative to thyroxine peroxidase antibodies (TPOAbs). Values of free thyroxin and thyroid-stimulating hormone (TSH) were compared with data from age- and gender-matched controls derived from the Nijmegen Biomedical Study, a population-based survey conducted in our hospital.We evaluated 159 patients. There were 111 males and 48 females. Median (IQR) age was 52 (40 to 62) years, serum creatinine concentration 99 (82 to 134) micromol/l, serum albumin concentration 29 (22 to 35) g/l, and proteinuria 6.6 (3.1 to 10.9) g/10 mmol creatinine. Median TSH was significantly higher in the patients than the controls (1.81 mU/l vs 1.34 mU/l, p.0.001); however, overt hypothyroidism was observed in only one patient.Patients with proteinuria have higher TSH levels, consistent with urinary loss of thyroid hormones. However, these urinary losses do not result in overt, clinically relevant, hypothyroidism. The role of subclinical hypothyroidism in these patients needs further evaluation.

We report a 62-year-old man with documented type 2 diabetes mellitus and hypertension, who presented with a rapid deterioration in renal function. The sudden decrease in renal function in this well-controlled diabetic patient prompted us to consider a nondiabetic and nonhypertensive cause. The urinary sediment showed a glomerular haematuria suggestive of glomerulonephritis. A diagnosis of fibrillary glomerulonephritis was made on renal biopsy. Fibrillary glomerulonephritis is a rarely diagnosed disease with clinical manifestations such as proteinuria, microscopic haematuria, nephrotic syndrome and impairment of renal function. A diagnosis of fibrillary glomerulonephritis can only be made by electronmicroscopy of the renal tissue. In this case report the spectrum of this disease is reviewed.

Patients with focal segmental glomerulosclerosis (FSGS) are considered to have a poor prognosis and spontaneous remissions are seldom reported. However, FSGS is not a single disease entity. Our aim was to describe the clinical course in initially untreated patients with recently diagnosed idiopathic FSGS.This was a retrospective study of patients with a diagnosis of FSGS by histology, who fulfilled the following criteria: proteinuria3.5 g/day, normal renal function, duration of proteinuria or hypertension of less than one year, normal-sized kidneys, no underlying renal disease, and a negative family history. Renal biopsies were reviewed without knowledge of the clinical course.Twenty patients (13 male, 7 female) fulfilled the study criteria. Median age was 49.3 (range 21.8 to 73.0) years, serum creatinine 90 +/- 20 micromol/l, proteinuria 10.0 +/- 5.5 g/day and serum albumin 24 +/- 6 g/l. After a median follow-up of 9.4 (2.1-18.6) years, 13 patients (65%) were in remission of proteinuria. Renal function deterioration occurred in seven patients, and prompted treatment in four of them. The ten-year death-censored renal survival was 89%. Renal function deterioration and remission rate could be predicted by selectivity index, serum albumin at three months after renal biopsy and the percentage of glomeruli with segmental sclerosis.Focal glomerulosclerosis is not a single disease. Case definition using strict clinical criteria identifies a subgroup of patients with idiopathic FSGS who have a good prognosis. In the majority of these patients immunosuppressive therapy is not warranted.

After cadaveric kidney transplantation, preservation-reperfusion damage results in glomerular and tubular proteinuria. There are no data on the time course of proteinuria after living-donor (LD) transplantation.In 10 patients receiving a kidney graft from an LD, the excretion of high molecular weight proteins (albumin, transferrin, and immunoglobulin G) and low molecular weight proteins (beta2-microglobulin and alpha1-microglobulin) was measured at various time points during the first 5 days after transplantation.Immediately after restoration of the circulation, we observed a massive nonselective high molecular weight proteinuria, indicative of glomerular damage. This proteinuria rapidly decreased to slightly elevated values beyond 24 hr after transplantation. Low molecular weight proteinuria, reflecting tubular damage, was also prominent and remained grossly abnormal even at day 5.After LD transplantation, preservation-reperfusion injury causes massive proteinuria during the first 24 hr. Thereafter proteinuria rarely exceeds 1 g per day.

We describe three patients with acute renal failure after the onset of gross haematuria. In all patients a presumptive diagnosis of rapidly progressive glomerulonephritis was made and immunosuppressive therapy initiated. A renal biopsy was performed in two patients, which showed evidence of IgA nephropathy. Extracapillary proliferation was seen in a few glomeruli. The most notable abnormality was acute tubular necrosis with intraluminal erythrocytes and cell debris. In the third patient, who was known to have longstanding glomerular haematuria, acute tubular necrosis was considered likely after review of the urinary sediment. Despite the fact that immunosuppressive therapy was stopped, renal function rapidly returned to normal in all these patients. We feel that our patients and additional literature data demonstrate that in patients with glomerular disease a reversible acute renal failure can occur that is caused by acute tubular necrosis mediated by haematuria. Recognition of this entity will prevent unnecessary long-term immunosuppressive therapy.

1. It has been reported that calcium antagonists lower blood pressure more effectively in salt replete hypertensive patients with a low plasma renin activity (PRA), whereas angiotensin converting enzyme (ACE) inhibitors are more effective in salt depleted patients with a high level of PRA. An inverse relationship between the antihypertensive effects of these two groups of drugs might therefore be expected. 2. Since salt retention and inappropriately high levels of PRA are said to contribute to hypertension in patients with chronic renal failure (CRF), an additive antihypertensive effect with both drugs might also be expected in such patients. 3. To test these hypotheses, we investigated the acute and chronic antihypertensive effects of the calcium antagonist nitrendipine and the new ACE inhibitor cilazapril, given alone, and in combination, in a double-blind, randomized, placebo controlled study of 11 hypertensive patients with chronic renal failure who had a mean pretreatment blood pressure of 149 +/- 3/96 +/- 2 mm Hg. Patients received nitrendipine 10 mg, cilazapril 1.25 or 2.5 mg depending on creatinine clearance, or placebo once daily orally. Nitrendipine and cilazapril were also combined at the same doses. 4. Nitrendipine and cilazapril were equally effective, with a maximal acute reduction of mean arterial pressure (MAP) of 5.3 +/- 1.8% and 8.0 +/- 1.9%, and after 1 week of treatment 5.0 +/- 2.4% and 8.1 +/- 1.8%, respectively. In individual patients no inverse relationship between the blood pressure responses to the two drugs was found.(ABSTRACT TRUNCATED AT 250 WORDS)