Long-term follow-up of patients presenting to adult nephrologists with chronic pyelonephritis and 'normal' renal function.

We studied the natural history, and therefore prognosis, of patients with chronic pyelonephritis presenting to adult nephrologists with a plasma or serum creatinine <90 mmol/l. From the Newcastle chronic pyelonephritis database, 255 patients with radiologically-proven disease were reviewed. Median follow-up was 95 months (95%CI 82. 3-109.3). Plasma creatinine was < or =90 micromol/l (P(Cr)< or =90 group) at presentation in 138. At presentation, hypertension, bilateral disease and proteinuria were less frequent in the P(Cr)< or =90 group (hypertension 19% vs. 32%, p<0.05; bilateral disease 25% vs. 70%, p<0.001; proteinuria 18% vs. 60%, p<0.001). With the exception of two patients, the renal prognosis of this group was excellent. Patients over the age of 18 years presenting to adult nephrologists with a diagnosis of chronic pyelonephritis and a creatinine < or =90 micromol/l can be reassured that the chances of developing end-stage renal failure in the future are very small. Most could be referred back to their general practitioner for long-term follow-up.

Heparin effect on ionised calcium concentration.

The effect of heparin on plasma ionised calcium was studied by adding it in increasing amounts to whole blood from 10 normal subjects. There was no significant change in ionised calcium from the addition of 1 U/ml but a significant fall of 0.02 mmol/l when 2 U/ml were added and a progressive further fall with increasing concentrations. Heparin from three different manufacturers produced similar results. The effect of heparinisation in vivo was studied during regular haemodialysis on 10 patients with chronic renal failure. Following intravenous injection of 10 000 U of heparin there was a consistent and significant fall averaging 0.03 mmol/l.

A method for the routine determination of aluminium in serum and water by flameless atomic absorption spectrometry.

A simple but reliable method for the routine determination of aluminium in serum and water by flameless atomic absorption spectrometry is described. No preparatory procedures are required for water samples, although serum is mixed with a wetting agent (Triton X-100) to allow complete combustion of the samples and to improve analytical precision. Precautions to prevent contamination during sample handling are discussed and instrumental parameters are defined. The method has a sensitivity of 35.5 pg and detection limits of 2.3 micrograms Al/l for serum and 1.3 micrograms Al/l for water. The method was used to determine the aluminium concentration in serum of 46 normal subjects. The mean aluminium content was 7.3 micrograms/l (range 2--15 micrograms/l.

Determination of serum ionised calcium by ion-exchange electrode in normal subjects.

Serum ionised calcium concentration [Ca2+] was measured with a calcium selective electrode in 65 normal people. A mean value of 1.06 mmol/l (+/- 0.04 S.D.) with an actual range of 0.97 to 1.13 mmol/l was obtained. Serum samples refrigerated at 4 degrees C for 24 h were satisfactory for analysis. Storage of whole blood samples for 6 h at room temperature before separation caused a very small error (+0.04 mmol/l). Mean results and ranges were similar in males and females and there was no significant correlation with age. No significant change in serum [Ca2+] was found following a normal meal. Serum [Ca2+] and total serum calcium showed a very slight correlation (r = 0.35). The method is reproducible and sensitive.

Serum calcium status in health and disease: a comparison of measured and derived parameters.

The relationship of serum ionised calcium to total calcium was investigated in three series of experiments, each using different ion-selective electrodes. In the first, total and ionised calcium were measured in healthy and patient groups to compare the predictive value of each estimation. In the second and third studies, measured ionised calcium was compared with ionised calcium calculated using 5 different formulae, and with total calcium, both uncorrected, and adjusted for varying protein content using eight formulae. In 144 of 149 healthy subjects, serum ionised calcium and total calcium were normal. There were discrepancies between serum ionised calcium and total calcium in 135 of 572 patients with conditions associated with abnormal calcium metabolism. Correction of total calcium, or calculation of ionised calcium did not significantly improve this figure. Thus, corrected or derived calcium values will not substitute for ionised calcium determination in patients with abnormal calcium metabolism.

A comparative evaluation of three high efficiency disposable dialyzers.

Until recently all disposable dialyzers have had a poorer overall performance than the best non-disposable dialyzer, the Meltec multipoint. The three disposables considered here (Gambro Lundia Nova, Cordis HFAK 4 and Rhone Poulenc RP 5) all have clearance of small molecules close to or, for the HFAK 4, just above that of the multipoint though their middle molecular clearance is not quite as good as the multipoint. The HFAK 4 has a better basal ultranfiltration rate but a poorer maximum ultrafiltration capacity. The RP 5 has a higher residual blood volume than the multipoint. In other respects the dialyzers are almost interchangeable and are reasonable alternatives to the multipoint in those centers which can afford single use disposable dialyzers.

Isolated C3 deposition in patients without systemic disease.

Deposition of C3 without immunoglobulins ("isolated C3") was found in 9.8% of 540 renal biopsies performed between 1976 and 1982. Thirty-two of these samples were from patients with systemic diseases (16), well defined forms of glomerulonephritis (9), other renal diseases (4) or renal allografts (4). The remaining 22 patients are described. Five had nephrotic syndrome, three of them with minimal changes on light microscopy and good response to corticosteroids. We were left with a group of 17 patients who presented with gross (4) or microscopic (12) hematuria or asymptomatic proteinuria (1) whose biopsies showed mesangial proliferation or/and hyperplasia and who followed a benign course over the mean 3 years of follow-up, with the exception of one whose renal function is declining. This clinicopathological picture is similar to that described in two previous publications suggesting that "Isolated C3 mesangial proliferative nephritis" is a recognizable sub-group within the spectrum of glomerulonephritis.

The association of renal amyloidosis with regional enteritis (Crohn's disease)--report of two cases and review of the literature.

Details of two patients with regional enteritis, whose condition was complicated by renal amyloidosis, are presented. The literature relating to the association is reviewed with special reference to the diagnosis, treatment and prognosis of renal amyloidosis.

Quadriceps tendon ruptures in uremia. Treatment with surgery and 1alpha-hydroxycholecalciferol.

Three young patients with chronic renal failure, one on regular hemodialysis, suffered bilateral quadriceps tendon ruptures. All three had uncontrolled, severe osteitis fibrosa. In two, aluminium hydroxide failed to control secondary hyperparathyroidism, while 1alpha-hydroxycholecalciferol (1alphaOHD3) given after the injury resulted in rapid resolution of the hyperparathyroidism. Prevention of tendon ruptures in uremia depends on effective control of secondary hyperparathyroidism. Treatment should involve prompt surgical repair and reversal of the osteitis fibrosa with an effective vitamin D metabolite such as 1alphaOHD3.

"Eosinophilic" peritonitis in continuous ambulatory peritoneal dialysis (CAPD).

Three cases of "sterile" peritonitis in CAPD patients are discussed, where the predominant white cell type in the peritoneal dialysis fluid was the eosinophil. No bacterial or fungal organism was isolated on repeated culture of the dialysis fluid and all had a benign course. The eosinophilic response appears to occur very soon after starting CAPD, is relatively asymptomatic and does not require antibiotic therapy. It is suggested that the eosinophilia is related to allergy to some constituent of the peritoneal dialysis system.

Pharmacokinetics of intravenous and intraperitoneal cefuroxime in patients undergoing peritoneal dialysis.

The pharmacokinetics of cefuroxime sodium, a parenteral beta-lactam antibiotic, were investigated in 9 patients during peritoneal dialysis. In 6 patients cefuroxime 500 mg was administered intravenously. Mean plasma levels of cefuroxime thereafter fell from 28.0 +/- 5.0 mg/l at 1 hr to 6.0 +/- 1.6 mg/l at 24 hr. Mean peak levels 4.6 +/- 1.9 mg/l in peritoneal effluent were found 7 hr after dosing and clearance of the drug by peritoneal dialysis averaged 4.7 ml/min. There was no evidence of net tubular secretion or of increased non-renal elimination. In 5 patients, the administration of cefuroxime, 100 mg/2 l dialyzate, in each cycle of dialysis maintained mean cefuroxime levels of 25.4 +/- 13 mg/l in the dialysis effluent. An average of 44% of the dose was not recovered in the effluent, and was presumably absorbed by the patient, and mean plasma levels of cefuroxime increased from 1.1 +/- 0.4 mg/l at 1 hr to 14.0 +/- 8.1 mg/l at 24 hr. If cefuroxime is used to treat peritoneal infections associated with peritoneal dialysis it should be given by both intraperitoneal and intravenous routes and followed up with parenteral therapy alone.

The relative roles of sodium and renin in the hypertension of renal disease. An assessment based on the response to frusemide and propranolol.

Twenty-seven patients with hypertension and varying degrees of renal failure were studied before and during the administration of frusemide. In 15 patients studies were repeated following the addition of propranolol. Mean exchangeable sodium was increased before the introduction of frusemide or propranolol in patients with azotemia, possibly due in part to the administration of other antihypertensive drugs, and was reduced to normal during frusemide treatment increasing slightly but significantly following the addition of propranolol. Blood pressure fell significantly with frusemide but there was no further significant fall with propranolol. The relationship of change in blood pressure to change in exchangeable sodium with frusemide did not reach significance. There was no relationship between changes in blood pressure and changes in plasma renin activity with frusemide, suggesting that the blood pressure response to frusemide is not limited by the rise in renin. The fall in blood pressure following the addition of propranolol was proportional to the dose of the drug but inversely proportional to the change in renin suggesting that renin levels are to some extent determined by the blood pressure response to propranolol rather than themselves determining that response. Serum creatinine was significantly increased during treatment with frusemide probably due to a combination of the effects of sodium depletion and the natural progression of the underlying renal disease rather than to nephrotoxicity. The further slight increase in serum creatinine following the addition of propranolol is in keeping with the reported effect of this drug on renal blood flow and glomerular filtration rate in patients without renal disease.

Serum proteins as indicators of poor dietary intake in patients with chronic renal failure.

A study of serum proteins in patients on regular hemodialysis has shown that many have low serum transferrin levels but near normal serum albumin and normal or raised pre-albumin levels. Hemoglobin values were related to transferrin levels. Low transferrin levels also occurred in patients with advanced osteitis fibrosa. Deficient protein intake seems the likely explanation. Measurement of pre-albumin does not reflect low protein intake in chronic renal failure; reasons for this discussed.

The natural history of renal function in untreated idiopathic membranous glomerulonephritis in adults.

Sixty-four patients (47 male, 17 females) aged between 20 and 70 years with idiopathic membranous glomerulonephritis, never having received steroid or immunosuppressive drugs prior to and subsequent to biopsy, have been followed to terminal renal failure or for a minimum of two up to fifteen years. Presentation was with asymptomatic proteinuria in 12 and nephrotic syndrome in 52. The serum creatinine at time of biopsy was less than or equal to 99 mumoles/l in 25, 100-119 mumoles/l in 18 and greater than or equal to 120 mumoles/l in 21. During the follow up there was no deterioration in renal function in 30 patients (48%). In 27 patients (43.5%) there was a steady deterioration in renal function, on the average 30 months (range 5-60) for the serum creatinine to double and 32 months (range 5-49) for the serum creatinine to reach 400 mumoles/l. In five patients there was a slow deterioration. A plot of the reciprocal of the sequential serum creatinine values with time indicates that the rate of deterioration is essentially constant in any patient but that there is a wide variation between patients. The reciprocal of the serum creatinine is a useful means of following the evolution of the disease. In two patients there was a change in the rate of deterioration and a cause could be identified (one with renal vein thrombosis, one with interstitial nephritis). Poor prognostic indicators were: nephrotic syndrome at presentation, impaired function at time of diagnosis, male patients and older age.

Formation of anti-N-like antibodies in dialysis patients: effect of different methods of dialyzer rinsing to remove formaldehyde.

Use of formalin to sterilize dialyzers is known to be responsible for the formation of anti-N-like antibody in long-term hemodialysis patients. Patients dialyzed as in-patients using formalin were found to be completely free of anti-N-like antibody, while among those on home dialysis, there was a high prevalence (31%) and incidence. The hospital patients were found to be receiving concentrations of formaldehyde less than 1 microgram/ml while those on home dialysis received 3-13 micrograms/ml. This is offered as an explanation for the absence of anti-N-antibody in patients using formalin-sterilized dialyzers.

Adverse effect of splenectomy in renal transplantation.

Between January 1968 and June 1974 at Newcastle upon Tyne, 63 patients underwent splenectomy in association with transplantation; 45 of these had splenectomy with bilateral nephrectomy before (20) or at the time of (25) transplantation; 18 had post-transplant splenectomy for leucopenia. Mortality was significantly higher in splenectomized patients than in 136 non-splenectomized controls. Of the 63 splenectomized patients, 25 died within 1 year of transplantation, 12 of severe infection associated with leucopenia. Although splenectomy produced a temporary rise in white cell count, leucopenia during the first year of immunosuppressive therapy was not significantly less frequent in splenectomized patients than in controls. There was no significant difference in graft loss between the splenectomy and control groups. It is concluded that splenectomy is contra-indicated in patients who are to undergo renal transplantation and confers no benefit when carried out because of leucopenia developing after renal transplantation.

Shunt nephritis: report of two cases and review of the literature.

We report two cases of glomerulonephritis associated with infection of cerebrospinal fluid shunts inserted for the treatment of hydrocephalus and comment an another 70 cases reported in the world literature. Although infection of CSF shunts is common, the development of glomerulonephritis is rare. Non-pathogenic bacteria are the commonest infecting organisms. Antibiotics are generally ineffective in eradicating the infection and the glomerulonephritis, but removal of the shunt is usually, though not always, associated with complete resolution of the renal disease.

Serum ferritin concentration: a reliable guide to iron overload in uremic and hemodialyzed patients.

The inter-relationships between serum ferritin, hemoglobin, serum iron and total body iron stores were studied in 20 patients with chronic renal failure treated conservatively and in 20 patients on regular hemodialysis. There was no relationship between serum iron or transferrin and bone marrow iron deposits, but serum ferritin concentration was a good indicator of increased marrow iron stores. All patients with serum ferritin levels above 300 microgram/l had increased iron stores. Serum ferritin assay is a useful non-invasive technique for detecting iron overload in uremic and hemodialyzed patients.

Aluminum in the dialysis fluid.

The major source of aluminum in patients with chronic renal failure treated by hemodialysis is the hemodialysis fluid. The aluminum is derived from both the water and the chemical concentrate used in the preparation of the hemodialysis fluid. Due to the complex physico-chemistry of aluminum in water and dialysis fluid, both the total aluminum concentration and the proportion of aluminum species able to cross the hemodialysis membrane may vary from water supply to water supply and from day to day within a supply. A "safe" level of aluminum in dialysis fluid, which will prevent aluminum transfer from dialysis fluid to blood, and promotes aluminum removal from blood, has yet to be determined.

1 alpha-hydroxycholecalciferol in hemodialysis renal osteodystrophy. Adverse effects of anticonvulsant therapy.

Two regular hemodialysis patients were assessed before, during and after therapy for 8 1/2 months with 1alpha-hydroxycholecalciferol (1alphaOHD3). The first patient (F.S.), treated with 2 mug daily, improved considerably with complete resolution of histological osteomalacia (O.M.), reduction in osteitis fibrosa (O.F.) and healing of Looser zones. The second patient (T.Y.), who was treated at the same time with a combination of phenobarbitone and phenytoin, showed no improvement while taking 3 mug of 1alphaOHD3 daily. It is suggested that hepatic microsomal enzyme inducing drugs antagonize the action of 1alphaOHD3 by interfering with its subsequent hepatic 25-hydroxylation.