The importance of oral foci of infection in renal transplantation

During the treatment of patients with renal failure or renal transplants the most important consideration is to eliminate sources of infection before and after the treatment. Acute or chronic oral infections or bacteraemias resulting from dental procedures may cause serious complications in these patients who already have lowered host resistance caused by immunosuppressant therapy. In order to determine the latest concepts from some international transplantation centres relating to the importance of and the effect of infective sources in the oral cavity, a survey form was prepared which included several questions related to oral foci of infection and renal transplantations.
Results obtained from 22 centres from 12 countries indicated that the majority of the centres included a dental examination in their routine protocol and required completion of any necessary dental treatment before transplantation. However, full agreement among all these centres on the necessity for dental examination as part of the protocol has not yet been reached.     

Renal acid excretion in early infancy

In early infancy, complex disorders of acid base metabolism are more frequent than in any other age group, with a predisposition to metabolic acidosis due to an age-related low renal capacity for acid excretion and an unphysiologically high actual renal acid load in nutrition with common formulas. Recently in preterm and small-for-gestational-age infants, persistent maximum renal net acid excretion (NAE) with subnormal or normal blood acid base status, impaired weight gain, and adaptive hormonal reactions have been observed. Incipient late metabolic acidosis is one example of a mixed disorder of acid base metabolism with maximum renal NAE in early infancy. Alkali therapy is highly effective and can be realized both on an individual basis, using urine pH screening as a diagnostic criterium for maximum renal acid stimulation, or on a general preventive level using modified standard formula with a reduced actual renal NAE similar to that seen on alimentation with human milk. From an integrated point of view, the low glomerular filtration rate and renal capacity for acid excretion beyond the developmental age of more than 44 weeks, may well be interpreted as the result of a specific adaptation to breast feeding sparing energy, and thus an evolutionary advantage for the survival of mother and child. Received July 10, 1996; received in revised form and accepted October 7, 1996     

Pharmacokinetics of ciprofloxacin and vancomycin in patients with acute renal failure treated by continuous haemodialysis.

To determine appropriate doses of ciprofloxacin and vancomycin for septic patients with acute renal failure (ARF) treated by continuous arteriovenous and venovenous haemodialysis, (CAVHD/CVVHD), we performed pharmacokinetic studies in patients receiving these antibiotics. All patients were treated by CAVHD/CVVHD using Hospal AN69S 0.43 m2 filters and Fresenius 1.5% peritoneal dialysis fluid at dialysate flow rates (Qd) of 1 and 2 l/h. Patients received ciprofloxacin 200 mg i.v. 12-hourly (n = 6) or 8-hourly (n = 5); vancomycin 1 g i.v. was administered to 10 patients approximately every 48 h to maintain therapeutic plasma levels. For ciprofloxacin, volume of distribution (Vdarea) was 136.5 +/- 9.81, terminal elimination half-life (t1/2) 6.4 +/- 0.8 h, and total body clearance (TBC) 264.3 +/- 22.9 ml/min (mean +/- SEM). Mean sieving coefficient (S/C) was 0.76 +/- 0.05 and filter clearances at Qd 1 and 2 l/h were 16.2 +/- 1.9 and 19.9 +/- 1.1 ml/min respectively. For vancomycin, Vdarea was 60.7 +/- 5.11, t1/2 24.7 +/- 2.6 h and TBC 31.0 +/- 4.6 ml/min. Mean S/C was 0.66 +/- 0.08 and filter clearances at Qd 1 and 2 l/h 12.1 +/- 2.0 and 16.6 +/- 2.0 ml/min. These data suggest that patients with ARF treated by CAVHD/CVVHD should be given ciprofloxacin 200 mg i.v. 8-12-hourly and vancomycin every 48 h.     

Prognosis of acute renal failure in children: a multivariate analysis

Various factors were analyzed in 80 consecutive children under 16 years who had acute renal failure (ARF), for various prognostic factors. Overall mortality was 42.5%, with significantly higher levels seen in hemolytic uremic syndrome (68%, P <0.05) and associated with cardiac surgery (90.9%, P <0.01). Anuria (67.6% vs. 43.5%, P <0.05), need for dialysis (85.3% vs. 56.5%, P <0.05), neurological complications (50% vs. 6.3%, P <0.01), and respiratory complications (35.2% vs. 2.1%, P <0.01) were significantly higher in nonsurvivors than survivors. Multiple regression analysis showed the presence of neurological and respiratory complications to be poor prognostic factors. Received May 2, 1995; received in revised form August 28, 1996; accepted September 13, 1996     

EFFECTS OF SARAFOTOXIN S6c ON RENAL HAEMODYNAMICS AND URINE FORMATION IN ANAESTHETIZED DOGS

1. The effects of sarafotoxin S6c (S6c), a selective endothelin ETB receptor agonist, on renal haemodynamics and urine formation were examined in anaesthetized dogs. 2. Intrarenal arterial infusion of S6c at a rate of 1 or 5 ng/kg per min produced a transient increase in renal blood flow (RBF), with no change in systemic blood pressure and heart rate; RBF then decreased gradually to below the basal value. There were significant and dose-dependent increases in urine flow and free water clearance and decreases in urine osmolality during S6c infusion, whereas urinary excretion of sodium and glomerular filtration rate (GFR) remained unchanged. Simultaneously, S6c administration elicited a marked increase in urinary excretion of nitric oxide (NO) metabolites, N0₂^? and N0₃^? (UNO*V). 3. In dogs simultaneously administered S6c (5 ng/kg per min) and iV^G-nitro-L-arginine (NOARG; 40 (jig/kg per min), a NO synthase inhibitor, the renal vasodilator effect of S6c was abolished and marked reductions in RBF and GFR were observed. The S6c-induced diuretic action was not affected by NOARG. In the presence of NOARG, there was a small amount of UNO_xV at the basal level and the administration of S6c did not increase UNOxV. 4. These results suggest that an intrarenal arterial infusion of S6c enhances the production of NO in the kidney and that this enhancement contributes to the peptide-induced renal vasodilation. In contrast, it is unlikely that S6c-induced water diuresis is related to NO production stimulated by this peptide.     

Non-immune therapy of IgA glomerulonephritis

Summary: The involvement of the IgA immune system and complement components in IgA glomerulonephritis (IgAGN) has prompted the use of immunosuppressive drugs in therapy, but none has so far been shown to alter the natural course of the disease. Because most patients with IgAGN present during the chronic phase of their illness, at the time when the initiating immune events may no longer be active, nonimmune therapy which targets the common pathway of progressive renal injury is likely to be more useful. There is increasing evidence that angiotensin-converting enzyme inhibitors (ACEI) reduce proteinuria and renal injury in patients with IgAGN, and this effect may be observed in both normotensive and hypertensive patients. Yet to be determined is whether this effect is specific for ACEI and whatever other effective antihypertensive drugs may achieve a similar result. Fish oil has recently been shown to retard the progression of renal failure in patients with aggressive IgAGN, but a narrow therapeutic window appears to exist for this form of treatment. Antiplatelet agents on their own appear to be ineffective but in combination with anticoagulation (low dose warfarin) have been shown to have an antiproteinuric effect and may preserve renal function in patients with progressive disease. Future directions of non-immune therapy of IgAGN include evaluation of the renoprotective effect of angiotensin II receptor antagonists, free-radical scavengers and antilipid drugs. More work should also be done to identify factors which put the patients at risk of developing progressive disease and which predict therapeutic response, as has been done recently with the identification of the deletion polymorphism of the angiotensin-converting enzyme gene as a marker of progressive disease and therapeutic response to ACEI in patients with IgAGN.     

Protein-loading test, urinary albumin excretion and renal morphology in diagnosis of subclinical diabetic nephropathy.

The acute effects of protein loading (1.5 g kg-1) on glomerular filtration rate (GFR) and urinary albumin excretion (UAE) were investigated in 23 type-I diabetic patients with no clinical nephropathy, and in 7 healthy subjects (controls). The results were compared with renal morphology data. In controls and in 14 diabetic patients (group 1) GFR increased by 27 and 37%, respectively, corresponding to normal renal reserve, but in 9 patients (group 2) GFR decreased by 20%, indicating the absence of a renal reserve. Microalbuminuria was found in none of the patients in group 1 and in 50% of patients in group 2. Two hours after the load UAE increased in all groups, but the increase was most marked in group 2, despite the fall in GFR. The two groups of patients did not differ with regard to the duration and control of diabetes, but differed markedly in terms of baseline GFR (131 vs. 195 ml min-1, P less than 0.01, in groups 1 and 2, respectively). Renal morphology showed minimal non-specific glomerular injury in group 1, and signs of glomerulosclerosis in group 2. We conclude that the impaired renal response to protein load precedes other subclinical manifestations of diabetic renal injury, and may be useful in the diagnosis of latent diabetic nephropathy.     

Type O Renal Glucosuria

ABSTRACT. We observed a 7-year-old boy with virtual absence of renal tubular glucose reabsorption (type O renal glucosuria). Glucose titration studies in his family revealed severe type A renal glucosuria in a younger brother, a mild type A defect in the mother and normal glucose reabsorption in the father; thus a spectrum of renal glucose transport defects was observed in members of the same family.     

Biochemical Modulation of 5-Fluorouracil with Murine Interferon-α/β Against Murine Renal Cell Carcinoma

Department of Urology, School of Medicine, Keio University, Tokyo, Japan
Background Conventional therapy for renal cell carcinoma using interferon (IFN) has shown limited antitumor action. The purpose of our study was to investigate synergistic antitumor effects of IFN and 5-fluorouracil (5-FU), and to elucidate the mechanisms of interaction between the 2 agents in mice.
Methods Antitumor effects and biochemical modulation of murine IFN-α/β and 5-FU were determined against the murine renal cell carcinoma cell line, Renca, in vivo. The activity of thymidylate synthetase and thymidine kinase was measured using cytosolic extracts of the tumors.
Results Combination treatment with IFN-α/β and 5-FU produced a significant enhancement of growth inhibition against Renca tumor. Treatment with 5-FU resulted in a 2.7-fold increase in the total amount of thymidylate synthetase and an 11.6-fold increase in the thymidylate synthetase inhibition rate, while the administration of IFN-α/β did not significantly reduce the 5-FU-induced increase in thymidylate synthetase. The administration of IFN-α/β decreased thymidine kinase activity to 65.5% maximally, compared with that in the control mice or the mice treated with 5-FU.
Conclusions The reduction of thymidine kinase caused by treating the mice with IFN-α/β changes the utilization of exogenous thymidine for DNA synthesis, and may represent the mechanism of the additive antitumor effect of the 2 agents, through the suppression of the salvage pathway for deoxythymidine monophosphate induction.     

Assessment of erythropoiesis following renal transplantation

Abstract: Ten patients, who received cadaveric kidneys, were followed for 24 wk with serial measurements of serum erythropoietin (S-Epo), transferrin receptor (S-TfR) and iron variables. The mean pretransplant creatinine clearance was 8.2 (range 0–22) ml/min and the mean haemoglobin (Hb) level was 99±18.6 (range 66–124) g/l. Nine patients demonstrated a gradual increase in S-Epo levels, which reached a peak, and was accompanied by a parallel increase in S-TfR levels with a median lag period of 3 wk between both peaks. Hb correction followed the S-TfR peak after a second lag period (median 7 wk). Elevated S-Epo and S-TfR did not result in correction of anaemia in 1 patient due to impaired graft function. Within 4 months, S-Epo levels reached the normal range while TfR levels were higher than normal. Follow-up of iron status demonstrated the development of iron deficiency in 5 patients, which was corrected spontaneously. Improvement in erythropoiesis after renal transplantation seems to occur by means of expansion of the erythroid marrow, as detected by increasing S-TfR levels, subsequent to a S-Epo peak. This expansion precedes Hb normalization. A nonuraemic environment is probably a prerequisite for the correction of anaemia but not for the increase in S-Epo or S-TfR levels. Iron deficiency may occur after transplantation due to an increase in iron utilization.