Contrast media-induced nephropathy: case report and review of the literature focusing on pathogenesis.

Contrast media administration during diagnostic and invasive procedures in high risk patients for nephrotoxicity is a common problem in clinical practice. The mechanisms involved in renal function impairment after contrast media administration are not precisely known but are intensively investigated, and new data have emerged in the literature lately. We present the case of a 72-year old male patient with diabetic nephropathy to whom a new generation iso-osmolar contrast medium (iodixanol) was administered during intravenous pyelography. Due to the contrast agent administration, the patient developed irreversible acute renal failure and became dialysis-dependent. This case suggests that even new generation contrast media (including iodixanol) may be severely nephrotoxic, when administered to high risk patients. Additionally we review the complex mechanisms involved in pathogenesis of contrast media nephrotoxicity.

Severe vitamin D deficiency in chronic renal failure patients on peritoneal dialysis.

UNLABELLED: The aim of this study was to evaluate the prevalence of vitamin D deficiency in chronic renal failure (CRF) patients on peritoneal dialysis (PD) and to correlate the findings with various demographic and renal osteodystrophy markers. METHOD: This cross-sectional, multicenter study was carried out in 273 PD patients with a mean age of 61.7 +/- 10.9 years and mean duration of PD 3.3 +/- 2.2 years. It included 123 female and 150 male patients from 20 centers in Greece and Turkey, countries that are on the same latitude, namely, 36-42 degrees north. We measured 25(OH)D3 and 1.25(OH)2D3 levels and some other clinical and laboratory indices of bone mineral metabolism. RESULTS: Of these 273 patients 92% (251 patients) had vitamin D deficiency i.e. serum 25(OH)D3 levels less than 15 ng/ml, 119 (43.6%) had severe vitamin D deficiency i.e., serum 25(OH)D3 levels, less than 5 ng/ml, 132 (48.4%) had moderate vitamin D deficiency i.e., serum 25(OH)D3 levels, 5-15 ng/ml, 12 (4.4%) vitamin D insufficiency i.e., serum 25(OH)D3 levels 15 - 30 ng/ml and only 10 (3.6%) had adequate vitamin D stores. We found no correlation between 25(OH)D3 levels and PTH, serum albumin, bone alkaline phosphatase, P, and Ca x P. In multiple regression analyses, the independent predictors of 25(OH)D3 were age, presence of diabetes (DM-CRF), levels of serum calcium and serum 1.25(OH)2D3. CONCLUSION: We found a high prevalence (92%) of vitamin D deficiency in these 273 PD patients, nearly one half of whom had severe vitamin D deficiency. Vitamin D deficiency is more common in DM-CRF patients than in non-DM-CRF patients. Our findings suggest that these patients should be considered for vitamin D supplementation.

Immunosuppressive therapy and clinical evolution in forty-nine patients with antineutrophil cytoplasmic antibody-associated glomerulonephritis.

Immunosuppressive therapy and clinical evolution were studied in 49 patients (29 females) with antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. The mean age of patients at presentation was 55 years, and the mean (+/-SD) follow-up was 43 months (+/-33) (range, 3-140). Among the 49 patients, 10 had biopsy-proven Wegener's granulomatosis, 33 microscopic polyangiitis, 2 Churg-Strauss syndrome, and 4 idiopathic crescentic glomerulonephritis. IgG ANCA autoantibodies were detected in all patients. Induction therapy included pulses and oral administration of methylprednisolone (MP) with oral administration of cyclophosphamide (CP) and plasma exchange in patients with alveolar hemorrhage and serum creatinine (SCr) levels >/= 6 mg/dL. CP was converted to azathioprine (AZA) or mycophenolate mofetil (MMF) after 3-6 months of therapy. Low doses of MP with or without AZA or MMF were administered until the end of follow-up. Therapy institution resulted in remission of disease in all patients. The mean SCr levels decreased from 4.9 mg/dL (+/-2.5) at the onset of the disease to 2.8 mg/dL (+/-1.7) (P > 0.0001), and 3.2 mg/dL (+/-2.3) (P > 0.0001) after 3 and 6 months, respectively. At the end of follow-up, 17 (35%) patients progressed to end-stage renal disease after 34 months (+/-29) (range, 3-98), and 30 (61%) patients maintained sufficient renal function. Two patient deaths were attributed to immunosuppression. Patients with high SCr levels at diagnosis and severe interstitial fibrosis found in renal biopsy had poor renal outcome (P > 0.01 and P > 0.02, respectively). Induction therapy with MP and CP seems to be the regimen of choice in patients with ANCA-associated glomerulonephritis. Early diagnosis and therapy institution as well as long-term treatment lead to acceptable renal survival.

Cyclosporine and its metabolites before and 2 h post-dose: comparative measurements of a monoclonal and a polyclonal immunoassay.

The aim of the study was to investigate the better accuracy of the 2-h post-dose (C2) levels of cyclosporine (CyA), compared with the pre-dose (C0) levels and to evaluate the results measured by a monoclonal or a polyclonal immunoassay. The parent compound of CyA in C2 (monoclonal2) was measured in 53 kidney transplant patients by the monoclonal fluorescence polarization method, as well as the parent compound plus metabolites (polyclonal2) by the polyclonal fluorescence polarization method. Also, the parent compound was measured in 21 of the patients for the C0 (monoclonal0), whereas the parent compound plus metabolites in 36, for the C0 (polyclonal0). As level of metabolites was considered the difference between polyclonal and monoclonal values (polyclonal-monoclonal), either in C0 (metabolites0) or in C2 (metabolites2). The ratio polyclonal2/monoclonal2 gave a mean value of 1.7+/-0.2 (mean+/-SD), whereas the mean value of the ratio polyclonal0/monoclonal0 was 2.3+/-0.6, with almost double variation. The mean value of the ratio metabolites2/monoclonal2 was 0.7+/-0.2 and of the ratio metabolites0/monoclonal0 was 1.3+/-0.6. The difference between the two ratios is very significant (p = 0.000001) and they are not correlated with each other (r = 0.18, p = 0.44). The measurements of monoclonal0 and polyclonal0 or monoclonal2 and polyclonal2 are very significantly correlated (r = 0.94, p = 0.000001 and r = 0.97, p = 0.000001, respectively). In C0 the proportion of metabolites is higher than in C2, with a double variation, as the degree of metabolism is diverse. Consecutively, in monoclonal methods, as cross-reactions occur with metabolites, it is more accurate to use the C2 measurement for the evaluation of CyA. The application of both methods, the polyclonal and the monoclonal, could be a useful tool as it gives an estimation of metabolites whose degree of contribution to the immunosuppressive result is difficult to ascertain. Finally, if for reasons of clinical experience, the polyclonal method is used, then the mean therapeutic levels of polyclonal2 are 1.5-1.7 compared with monoclonal2.

Acute renal failure--which treatment modality is the best?

Despite the progress in animal research concerning the pathophysiology and the progress in clinical practice regarding the methods of therapy, the incidence and mortality of acute renal failure remain high, especially when other organs are involved. New pharmacological interventions have led to the perspective that in the near future it may be possible to prevent and/or ameliorate this devastating syndrome. Continuous dialysis therapy and the selection of a biocompatible membrane may possibly help the critically ill patient especially when parenteral nutrition and correction of electrolyte and acid-base disturbances are important. Nevertheless, more solid data are needed and one should take into consideration that acute renal failure is a multifactorial syndrome. The type of dialysis itself is not the only matter which has to be evaluated since the mortality rate can be correlated with the number of involved organs before or after the initiation of acute renal failure and with the severity of the original disease. In clinical practice, a large number of prospective studies and more sophisticated statistical methodology are needed in order to evaluate the proper treatment modality.

Acute renal failure in a medical setting: changing patterns and prognostic factors.

The clinical characteristics of 118 patients (60 male) with acute renal failure (ARF) admitted between 1980 and 1991, were retrospectively analyzed and compared with our earlier series of the 1960s. The mean age was 53 years (16-82 years). There was a marked decline in the hypotension-related cases (43% vs. 17%, p < 0.01) and a concomitant increase in the nephrotoxic cases (5% vs. 17%, p < 0.005) in recent years. The number of ARF cases significantly decreased after 1986 (31%) compared to the pre-1986 era (69%, p < 0.001). A complete (35%) or partial recovery (55%) was the rule in the majority of the patients. The overall mortality was 27%, virtually unchanged in comparison to the 1960s (30%). However, a tendency toward lower mortality was seen after 1986 (17%) in comparison to before (32%, p < 0.05). Sepsis and cardiovascular complications were the leading causes of death. Fewer deaths were observed among younger patients (< 30 years, 12.5%) compared to middle-aged patients (30-59 years, 34%, p < 0.05) and to these older than 60s (53.5%, p < 0.002). Also, deaths were rare in patients with only renal involvement (6%), increasing to 30% when 2 vital organ systems were affected (p < 0.005) and to 67% in cases with multiple organ failure (p < 0.001). Early institution of dialysis and the nonoliguric forms of the syndrome seem to be associated with better prognosis. In conclusion, the incidence of ARF has declined in recent years, with a concomitant tendency towards lower mortality. Death rate is mainly determined by the age and the number of organ involvement. Early dialysis seems to contribute to the lower mortality seen in recent cases.

Cyclophosphamide provides no additional benefit to steroid therapy in the treatment of idiopathic membranous nephropathy.

Thirty-six patients with idiopathic membranous nephropathy were retrospectively studied. The mean age was 47 years and the male to female ratio 25 to 11. Twenty-eight patients (77.8%) had nephrotic syndrome at first investigation. Nineteen patients received corticosteroids alone (group A) and 17 received corticosteroids combined with cyclophosphamide (group B). The mean period of follow-up was 58.9 months (range, 12 to 156 months). The two groups did not differ in clinical or laboratory features at the time of biopsy or at the start of treatment. In the entire series a complete remission of proteinuria occurred in 13 of 36 patients (36.1%) and a partial remission occurred in 13 (36.1%); 10 patients (27.8%) had no response. Optimal remission of proteinuria was usually recorded 6 to 12 months after the start of treatment. The two groups showed no statistical differences regarding the rate of complete (seven v six patients; P = not significant) or partial (six v seven patients; P = not significant) remissions. Two patients (one from each group) entered end stage renal failure during follow-up. At last assessment, the number of patients with complete remission (four v three patients; P = not significant), nonnephrotic proteinuria (nine v nine patients; P = not significant), or nephrotic syndrome (five v four patients; P = not significant) was similar in both groups. In addition, final plasma creatinine did not differ significantly between the two groups (1.8 +/- 2.3 mg/dL v 2.6 +/- 2.6 mg/dL; P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Idiopathic retroperitoneal fibrosis: a long-term follow-up study.

Eleven patients (8 male) with idiopathic retroperitoneal fibrosis (IRPF) were reviewed. The mean age of the patients was 44 years. Five patients (group 1) who had moderate obstruction were treated only by steroids. Six patients (group 2) who presented with severe obstructive uropathy (and/or serious metabolic disturbances) were treated with a combination of surgery and steroid administration. Unilateral or bilateral ureterolysis was performed in 5 patients. It was associated with nephrostomy in 2 cases and intraperitoneal disposition of the ureters in 1 case. Left nephrostomy without ureterolysis was performed in 1 patient. The mean follow-up period was 5.5 years (5 months to 20 years). All patients of group 1 now have normal renal function. In 5 patients of group 2, renal function improved significantly after operation; one of them was started on regular dialysis 16 years later. In another patient, IRPF recurred in the ureter of a living related renal graft 6 months after transplantation. In conclusion, steroid treatment alone offers a long-term survival in patients with IRPF of moderate severity. Combined treatment must be recommended for patients who present with severe obstruction and advanced uremia.

Cancer in renal transplant recipients.

The incidence of cutaneous malignancies and non-Hodgkin lymphomas is higher in transplant recipients than in the general population. From 1968 to 1984, 200 kidney grafts were transplanted to 180 patients with end-stage renal disease. All patients were on azathioprine (Aza) and prednisolone. In selected cases ALG and/or small doses of CsA were added. Six patients developed malignant tumors (two Kaposi sarcoma, one squamous cell and one squamous plus basal cell skin cancers, one reticulosarcoma, and one glioma). Mean age of patients was 43 years (range 35-53 years), and mean time of appearance of the tumor after transplantation was 62 months (range 24-98 months). Treatment consisted of reduction of the dosage of Aza, surgical removal or local irradiation of the tumor, and chemotherapy in case of systemic involvement (two cases). Three patients died (one Kaposi sarcoma, one reticulosarcoma, and one glioma) 3 to 6 months after diagnosis, and all three had previously been on high doses of Aza. The remaining three cases (one Kaposi) were cured by stopping or decreasing Aza, by excision, and/or local irradiation of the tumor. It seems that late diagnosis and Aza in high dosage are the main factors leading to the rapid dissemination of the initially localized tumor.

Urinary tract infections after renal transplantation.

From 1980 to 1983, 69 patients (36 male) with end-stage renal disease underwent kidney transplantation (11 from cadaveric donors). Twenty-six out of 69 (17 male) with a mean age of 37 years (range 16-50 years) developed 69 UTI episodes. The standard immunosuppressive regimen consisted of prednisolone and azathioprine and, in selected cases, antilymphocyte globulin or cyclosporin A were given for a short period of time. Thirty-five episodes (50%) occurred within two months of the operation. The most commonly isolated bacteria were E. coli (28 cases), Ps. aeruginosa (16) and Proteus mirabilis (9). Kidney graft dysfunction, diabetes mellitus, urological complications and antirejection treatment were the main predisposal factors. Recurrence or reinfections were finally diagnosed in 19/26 patients (73%). Thirteen patients presented with asymptomatic bacteriuria (55% of episodes). Aminoglycosides, ureidopenicillins and third-generation cephalosporins were found to be very effective for treating severely ill, febrile patients. In addition, trimethoprim/sulphamethoxazole and mecillinam were useful for patients on long-term chemotherapy. There were no deaths or impairment of the renal graft function directly attributable to the urinary infection. In conclusion, UTIs are a very common cause of morbidity in kidney graft recipients, with the highest incidence in the early post-transplant period. Recurrences or reinfections occur often and asymptomatic bacteriuria is a common finding which needs not be treated aggressively in the absence of symptoms or obstructive uropathy. Patient and graft survival in the long term remain unaffected by the presence of the urinary infection.

The effect of spironolactone in hypertensive patients on regular haemodialysis and after renal allotransplantation.

To determine the role of the renin-angiotensin-aldosterone system in the maintenance of hypertension in patients with end stage renal disease, twenty four hypertensive patients were studied on regular haemodialysis treatment (RDT) and after successful kidney transplantation. The first group consisted of nine patients on RDT with their own kidneys in situ, and the second group consisted of nine kidney transplants. All 18 patients were given spironolactone 300 mg daily for three weeks following a control period of the same duration. In addition, three anephric patients on RDT were studied with the above protocol and three other patients on RDT were given the same dose for only six days. Blood pressure (BP), body weight, plasma K-Na, aldosterone and renin activity in all patients, and Na and aldosterone in urine in the second group were measured. In the first group of patients on RDT plasma potassium and renin activity increased significantly but BP remained unchanged. In the second group of transplanted patients plasma potassium, renin activity, and aldosterone were increased and BP diminished significantly. In the group of three anephric patients plasma potassium increased but plasma renin activity remained very low. Finally, in the patients on dialysis who received spironolactone for only six days there was a parallel increase of serum potassium and plasma renin activity. These findings suggest that in patients on RDT spironolactone stimulates renin secretion and potassium retention possibly by an effect on the remaining nephrons and/or the intestinal wall. On the contrary, in the transplanted patients the effect of spironolactone on the renal tubule is capable of producing sodium depletion and fall in BP.

Response of uremic osteoid to vitamin D.

Three patients with nutritional osteomalacia and three with the osteomalacia of chronic renal failure were treated with small doses of vitamin D for 4 to 10 months. The plasma concentration of 25-OH vitamin D rose to and remained within the normal range throughout the study. There was similar increase in the extent of calcification front in the osteoid lamellae lying immediately adjacent to calcified bone in the two groups of patients. The associated histologic appearances of hyperparathyroidism improved in the patients with nutritional osteomalacia but did not change or became worse in the patients with the osteomalacia of chronic renal failure.

The 'shrinking man' syndrome.

3 men presented with loss of height. Quantitative bone histology revealed all the features of hyperparathyroidism, yet the plasma calcium and hand radiographs were normal. 2 of the patients had been on maintenance haemodialysis for over 10 years (a group in whom osteopenia is described) and the third was elderly. It is probable that in these 3 patients the loss of height was due to wedging of vertebrae as a result of the hyperparathyroidism. It is suggested that in all 3 the disease became manifest clinically because the vertebrae may have been osteopenic for other reasons.

The role of parathyroidectomy in the management of hyperparathyroidism in patients on maintenance haemodialysis and after renal transplantation.

Between March 1964 and March 1980, 36 (34 dialysis, 2 transplant) of 327 patients accepted for the maintenance dialysis/transplantation programme at Charing Cross Hospital were submitted to parathyroidectomy. There were four main indications: persistent hypercalcaemia, progressive phalangeal erosions, aseptic necrosis of the femoral head and height loss with abnormal bone biopsy despite normal hand radiographs. At parathyroidectomy, 4 glands were removed in 1 patient, 3 1/2 glands in 24, 3 glands in 7, 2 glands in 3 and a single large gland in 1 patient. The operation was followed by improvement in 28 patients, no change in 5, and progression of hyperparathyroidism in 3.2 of the 28 patients who improved later relapsed and were treated with 1,25-(OH)2 vitamin D3. 4 patients were submitted to a further parathyroidectomy and improved considerably. We would conclude that, although parathyroidectomy is an effective and safe procedure, it is to be hoped that careful monitoring of bone state and early administration of 1,25-(OH)2 vitamin D3 may reduce the need for parathyroidectomy.

Double-blind trial of oral 1,25-dihydroxy vitamin D3 versus placebo in asymptomatic hyperparathyroidism in patients receiving maintenance haemodialysis.

Fifty-seven patients who had been receiving maintenance haemodialysis for a mean of 4.6 years were given 0.25-0.5 microgram oral 1,25-dihydroxy (1,25-(OH)2) vitamin D3 or a placebo in a double-blind manner for one to two years. In patients with normal radiographs (mean plasma parathyroid hormone concentration 205 microliterEq/ml) 1,25-(OH)2 vitamin D3 prevented the development of the radiological appearances of hyperparathyroidism. In patients with abnormal radiographs (mean plasma parathyroid concentration 709 microliterEq/ml) 1,25-(OH)2 vitamin D3 arrested or reversed the radiological changes of hyperparathyroidism. Nevertheless, the response was slow and the concentration of the hormone remained considerably raised (mean 445 microliterEq/ml). It is concluded from these results that giving 1,25-(OH)2 vitamin D3 to patients receiving maintenance haemodialysis who have normal hand radiographs or minimal erosions is beneficial. In patients with more advanced hyperparathyroidism parathyroidectomy should be considered unless there is a rapid response.