Hans Erik Hansen

Prognosis and risk factors in acute, dialysis-requiring renal failure after open-heart surgery.

Of 1988 patients who underwent open-heart surgery from 1980 through 1988, 68 (3.4%) developed postoperative acute renal failure requiring dialysis (2.5% of adult and 8.3% of pediatric patients). Isolated aortocoronary bypass grafting was the operation with lowest incidence of this complication (0.6%). Acute renal failure usually appeared during the first 3 postoperative days. It carried a mortality rate of 63%, with half of the deaths occurring during the first few postoperative days, due to low cardiac output and progressive multiple organ failure. Logistic regression analysis in cases of aortic valve replacement demonstrated that significant independent preoperative risk factors for acute renal failure were renal insufficiency (serum creatinine greater than 110 mumol/l in greater than or equal to 2 samples) and increased cardiothoracic index/left ventricular end-diastolic dimension. Data from the literature indicated no time-related trend towards reduction of acute renal failure incidence or mortality. Prevention of low cardiac output is of major importance in these respects. Operative intervention before development of advanced disease with left ventricular dilatation and secondary kidney failure is advocated.

Renal Toxicity of Lithium

SummaryLithium is a valuable psychotropic drug, but its therapeutic index is low. As the lithium ion is almost exclusively eliminated by the kidneys, reduced renal lithium elimination may lead to increasing serum lithium levels and lithium intoxication. Since lithium intoxication may be complicated by acute renal insufficiency, which will further delay lithium elimination, a ‘vicious circle’ can be established. Fluid therapy of any kind has been shown to have only a very limited effect on renal lithium elimination during lithium intoxication. The most efficient method for eliminating lithium from the body is through haemodialysis treatment. Peritoneal dialysis is slower but also effective. Dialysis treatment has to be carried out long enough to ensure a serum lithium concentration of less than 1mmol/L after equilibrium between intracellular and plasma lithium is established.Lithium intoxication is often preceded by events leading to decreased fluid intake and/or increased extrarenal water and sodium loss. However, treatment with large amounts of sodium chloride should be avoided so as not to induce a condition of hypernatraemia in patients with severely impaired renal concentrating ability, which is commonly seen during and after acute lithium intoxication. Reduced renal concentrating ability is also a common complication with long term lithium treatment even without overt intoxication. As in the situation of intoxication, this condition makes the lithium-treated patient more susceptible to dehydration due to reduced fluid intake and/or increased extrarenal water and sodium loss. The reduction in renal concentrating ability is of renal, not hypothalamic, origin since plasma arginine-vasopressin concentrations are increased in patients with lithium-induced impairment of renal concentrating ability, and the hypothalamic region in these patients reacts to stimuli such as water deprivation and water loading. The impairment of renal concentrating ability is correlated to the duration of lithium treatment or to the product of serum lithium concentration and the duration of lithium treatment. The impairment of renal concentrating ability parallels histological damage to the tubules. Reduced renal concentrating ability is the most prominent lithium-induced renal lesion, since glomerular filtration rate is normal or almost normal in the majority of the patients, as is renal albumin excretion. Normal or almost normal β2-microglobulin excretion excludes any severe constant toxic action on the proximal tubules. Thus, the lithium-induced renal lesion is located in the distal part of the nephron where the highest lithium concentrations are present. Histologically, tubular lesions, cystic tubular dilatation or cysts characterise the lithium-induced nephropathy, but the origin of the fibrotic changes is still debatable, since such changes have also been found in manic-depressive patients who have not been treated with lithium.It is unlikely that lithium-induced nephropathy will cause severe renal failure or terminal uraemia. The changes in renal function which may develop during long term lithium treatment should not result in unnecessary anxiety and do not contraindicate lithium treatment. Nevertheless, lithium therapy should be used only for severe mood disorders, and certainly lithium treatment should be efficiently controlled in order to avoid lithium intoxication, which can result in sudden deterioration in renal function, and which is the most important complication of long term lithium treatment. Patients should be warned about the dangers of dehydration, and from the initiation of treatment should drink not less than 2 to 3L of fluid per day in order to minimise lithium concentrations in the distal part of the nephron.

Short and long term outcome in a consecutive series of 419 patients with acute dialysis-requiring renal failure

UNLABELLEDnThis analysis was done in a consecutive series of 419 patients with potentially reversible acute renal failure (ARF) requiring dialysis treated during the 12 year period January 1977 to December 1988. The aims were to describe the relationship between morbidity, mortality, and the year of admission, to evaluate the effects of various follow-up periods and stratification on main prognostic factors, and to report long term survival.nnnRESULTSn1) There was a significantly higher (p < 0.001) number of organ failures/patient in the last 6 year period compared with the first 6 year period. 2) Early (day 90) mortality was 46% and did not change significantly during the 12 year period. 3) Etiology, age of the patient, and the severity and the progression of the underlying disease were the most important factors determining outcome. 4) Time of censorship and stratification of the patients influenced prediction models. 5) Estimated 5 year survival rate was 52% (95% confidence limits 44-60%) in patients with a medical etiology, and 28% (95% confidence limits 20-36%) in patients with a surgical etiology.nnnCONCLUSIONSn1) Prognosis did not change significantly during the 12 year study period, and was almost solely dependent on the severity and progression of the underlying disease process. 2) Changed censoring time and stratification were important tools for enhancing the yield of information from the study. 3) The time(s) and method(s) of risk scoring, stratification(s) of patients, the time(s) of censorship on vital status, and the method for statistical analysis have to be identical if results of treatment for ARF from different centers should be compared.

Changes in Renal Volume During Normal Pregnancy

Twenty‐four healthy pregnant women with a normal pregnancy demonstrated a significant uniform enlargement of both kidneys. The renal volumes increased by a maximum of 30% during pregnancy. However, this could not be attributed to hydronephrosis, as the patients were selected in such a way that none with pelvectasia participated in the study. All regained normal renal volume within the first week after delivery. It is well known that a glomerular hyperfiltration takes place during normal pregnancy. Possible pathogenetic mechanisms are discussed.

Morphologic renal changes during cyclosporine treatment of psoriasis: Studies on pretreatment and posttreatment kidney biopsy specimens

BACKGROUNDnBecause of concern about long-term renal toxicity from low-dose cyclosporine therapy, we studied kidney biopsy specimens in psoriasis patients treated with this drug.nnnOBJECTIVEnThe purpose of the study was to investigate whether any morphologic changes appear after approximately 1 year of treatment.nnnMETHODSnPretreatment and posttreatment renal biopsy specimens were performed in 12 psoriasis patients treated with cyclosporine in dosages from 1.8 to 6 mg/kg/day for 6 to 18 months.nnnRESULTSnThe study disclosed a slight but significant increase in interstitial fibrous tissue, which negatively correlated with creatinine clearance. The findings were similar to those described in patients receiving higher dosages of cyclosporine.nnnCONCLUSIONnThe clinical relevance of these so-far minor changes is unknown and does not exclude the use of cyclosporine in severe psoriasis; however, they should be taken into consideration in so-called low-dose therapy.

Segmental localization and quantitative characteristics of tubulitis in kidney biopsies from patients undergoing acute rejection

The term tubulitis denotes infiltration of the renal tubular epithelium by mononuclear cells. Tubulitis is one of the most reliable signs of acute renal allograft rejection. However, its segmental localization and quantitative characteristics are not precisely known. To investigate this question, formalin-fixed kidney biopsy specimens from 15 patients with transplanted allografts undergoing acute rejection were studied stereologically by identifying cortical tubules with segment-specific markers. The periodic acid-Schiff reaction, peanut lectin, and antibodies against Tamm-Horsfall protein and epidermal cytokeratins, all applied to the same section, were used to identify the profiles of proximal tubules (PTs), distal convoluted tubules (DCTs), distal straight tubules (DSTs), and the cortical collecting system (CCS, connecting tubules and cortical collecting ducts), respectively. Two parameters, the relative intrasegmental length and the average intensity of tubular damage, were determined to describe the degree of tubulitis quantitatively. Tubulitis was most prominent in the DCTs, followed by the CCS. The average intensity of tubulitis was lowest in the DSTs. The results indicate that the PTs are not the main site of tubulitis, despite the fact that they are regarded primary targets of the rejection response.

Prognosis in Septicemia Complicated by Acute Renal Failure Requiring Dialysis

During a 12-year period 419 patients were admitted because of acute renal failure requiring dialysis. Fifty (12%) had septicemia verified by blood culture. In a retrospective study age, sex, focus of infection, blood culture results, kidney function, mode of dialysis treatment, numbers and durations of complicating organ failures, presence of gastrointestinal bleeding, and secondary complicating events of septicemia were recorded for the purpose of establishing a prognostic index based on clinical criteria. Respiratory failure was present in 34 patients, circulatory failure in 31 patients, failure of coagulation system in 25 patients, and hepatic failure in 10 patients. Overall mortality was 46%. Highest death-rates were found during the first days of dialysis. In patients with multiple organ failures, in elderly and in patients suffering from staphylococcus aureus septicemia, a non-significant trend towards higher mortality was found. The mode of dialysis treatment did not influence patient survival. Our intention of establishing a prognostic index based on bedside clinical criteria has not been fulfilled. Even though mortality-rate increases in patients with acute renal failure complicated by failure of one or more vital organs, survival-rate in patients with four or more organ failures was 30%.

Acute tubulointerstitial nephritis: phenotype of infiltrating cells and prognostic impact of tubulitis

The prognostic impact of tubulitis and the phenotype of the infiltrating cells in the tubules were studied in ten percutaneous renal biopsies from six patients with acute tubulointerstitial nephritis (ATIN). The inflammatory cell subsets in the tubules and interstitium (CD3+, CD4+, CD8+, CD20+, CD45RO+, CD56+, CD57+, CD68+ and TIA-1+ cells), the expression of vimentin and the proliferation-associated antigen Ki-67 by cortical tubular cells, and the grade of tubulitis, interstitial infiltration and fibrosis were analysed. Cytotoxic injury to tubular cells in the vicinity of tubular-wall-localized lymphocytes was studied ultrastructurally. ATIN was drug-induced in three patients, related to Legionella infection in two and idiopathic in one patient. Four patients recovered, one with reduced renal function. Two patients developed end-stage renal disease. CD8+ and CD4+ lymphocytes, and a smaller number of macrophages, infiltrated the tubules. The predominant lymphocyte subset in the tubules was the same as in the interstitium. Cytotoxic injury to tubular cells was not seen electron microscopically. The tubular cells exhibited increased proliferative activity and expressed vimentin, indicating non-specific tubular damage. The cell subset, the severity of tubulitis, and the tubular expression of vimentin were not related to outcome. the main prognostic factor was the severity of the interstitial fibrosis. Tubulitis in ATIN may be a harmless non-immune reaction, mediated by tubular expression of cytokines, together with adhesion and other molecules.

Acute Renal Failure Caused by Polymyxin B Containing Ointment

A case is presented in which a 67-year-old man suffering from non-insulin-dependent diabetes mellitus, after being treated with polymyxin B containing ointment for leg ulcers, developed acute renal failure. After a period of 13 days during which the patient was treated with peritoneal dialysis 5 times, renal function returned. At discharge creatinine-clearance was 12 ml/min. Treating large ulcers with polymyxin B may be dangerous.