Role of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in the prevention of progression of renal disease.

Systemic hypertension is common in patients with acute as well as with chronic renal diseases. Hypertension is an important factor that contributes to the progression of renal failure. Cardiovascular disease is the leading cause of death and disability in patients with chronic renal failure and in those receiving renal replacement therapy. The prevalence of hypertensive nephropathy remains unabated. Hypertension and chronic renal failure are closely interlinked and govern the morbidity and mortality in patients afflicted by these conditions. There is considerable hope that effective control of hypertension may retard the progression of renal disease. Although mere control of hypertension is of paramount importance, specific pharmacologic approaches may offer certain important renal advantages. Angiotensin-converting enzyme (ACE) inhibitors, by the virtue of their intrarenal effects, exert favorable consequences on the kidney function (and structure, to some extent), particularly in patients with diabetic nephropathy and hypertension. Both experimental and clinical studies have demonstrated the renoprotective effects of ACE inhibitors; these drugs slow down the progression of renal disease independent of their antihypertensive actions. More recently, angiotensin-receptor blockers have been shown to exert similar glomerular effects as ACE inhibitors. Preliminary clinical data also suggest a possible role for angiotensin-receptor blockers in the prevention of progression of renal failure. Therapeutic agents that inhibit the renin-angiotensin axis hold considerable promise in the management of patients with renal disease by slowing down the rate of decline in renal function.

The role of tacrolimus in adult kidney transplantation: a review.

The use of tacrolimus (FK506) in adult kidney-transplant recipients has been the subject of a number of single- and multi-center studies. This review article focuses on those studies in which tacrolimus was used either as rescue therapy in patients who developed refractory rejection on cyclosporine (CyA)-based regimens or as primary immunosuppression in adult renal-allograft recipients. Twenty-five prospective and retrospective studies conducted in the US, Japan and Europe, including single- and multi-center experiences, were identified in the medical literature. Of these studies, most show a 74-98% initial success rate for tacrolimus rescue therapy. Comparative studies reviewed herein demonstrate comparable patient- and graft-survival rates between tacrolimus- and CyA-treated patients. Many studies have shown that rejection episodes occur with similar or lower frequency among patients treated with tacrolimus than among those given CyA as primary immunosuppression. The major toxicities associated with tacrolimus are nephrotoxicity, neurotoxicity and diabetogenicity. Results from several studies have also demonstrated an association between these tacrolimus side effects and high whole-blood trough levels of tacrolimus. In many cases, a reduction in dosage can reverse these adverse effects. In summary, based on both single- and multi-center data, tacrolimus has been demonstrated to be efficacious when used for either primary immunosuppression or as rescue therapy for refractory acute rejection in adult renal-allograft recipients.

Paraparesis due to massive ectopic paravertebral calcification in a patient on maintenance hemodialysis.

Secondary hyperparathyroidism is ubiquitous in patients with end-stage renal disease who are on dialysis. We report a dialysis patient with an unusual manifestation of hyperparathyroidism. Initially, the patient was misdiagnosed to have clavicular osteomyelitis. The underlying hyperparathyroidism was not recognized, only to be discovered later, when the patient presented with spastic paraplegia and massive ectopic calcification in the cervical spine. The patient made a complete recovery following surgical resection and parathyroidectomy.

Single center experience of the effect of delayed function on outcome in retransplant recipients of cadaveric renal allografts.

The incidence of DRF in the regraft study group was most commonly seen in patients with a historic high level of HLA sensitization. Primary NF was an immune mediated event seen in 63% of third regrafts. Delayed use of CyA with ALG induction coverage provides good graft survival with either double or triple maintenance therapy. Stricter patient selection for third transplants and aggressive clinical monitoring of the regrafted patient has provided a 1-year actuarial graft survival result of 88% at our transplant center.

A randomized trial comparing double-drug and triple-drug therapy in primary cadaveric renal transplants.

A controlled trial was carried out in 209 primary cadaveric renal transplants to compare the effects of cyclosporine and steroids (double therapy) with those of cyclosporine in lower initial dose, azathioprine, and steroids (triple therapy). Patients have been followed 1-36 months since transplantation. Actuarial two-year graft survival (double 74%, triple 76%) and two-year patient survival (double 90%, triple 93%) were similar for both groups. Further analysis of particular risk factors including age, diabetes, HLA matching, acute renal failure, and use of sequential Minnesota antilymphocyte globulin in patients with delayed graft function also showed similar outcomes with both immunosuppressive regimens. Initial hospitalization time, rate of rejection, incidence of serious infection, and rate of rehospitalization were not different. Mean CsA doses and mean trough whole-blood levels were higher in double-therapy patients at hospital discharge but not by three months posttransplant. There were no differences between the two groups in iothalamate clearance at any time. Hypertension was more frequent six months posttransplant in the triple-therapy group (p less than 0.05). Thus, similar results were obtained with both regimens, and except for hypertension no regimen appeared to have increased side effects up to three years posttransplant.

Effect of 1,25-(OH)2D3 on jejunal absorption of magnesium in patients with chronic renal disease.

These studies were performed to see if jejunal malabsorption of magnesium in patients with chronic renal disease was influenced by therapy with 1 alpha, 25-dihydroxyvitamin D3 [1,25-(OH)2D3; 2 microgram/day by mouth for 7 days]. This treatment restored normal serum concentrations of the vitamin D metabolite from 0.9 +/- 0.2 to 4.2 +/- 0.6 ng/dl. Jejunal absorption of magnesium, measured by a triple-lumen constant-perfusion technique, was enhanced in each of the seven patients by this therapy. The mean value rose from 0.04 +/- 0.02 to 0.13 +/- 0.02 mmol . 30 cm-1 . h-1. This last value is similar to the magnesium absorption rate in untreated normal subjects. These results demonstrate that magnesium absorption in the human jejunum is dependent on vitamin D, and they show that 1 alpha,25-dihydroxyvitamin D3 therapy in patients with chronic renal failure is associated with an enhanced jejunal absorption of magnesium.

Rubella antibodies and adverse events late after renal transplantation.

Rubella antibody titers were determined pretransplant and then serially posttransplantation in 52 consecutive patients whose renal allografts survived at least three months. Group A patients (18) had antibody titers greater than or equal to 1:128 in the posttransplant period. Group B (24) had intermediate antibody titers that never rose higher than 1:64. Group C (10) consistently had antibody titers less than 1:8. Group A did not differ from groups B and C with respect to age, race, sex, type of transplant, underlying renal disease, or maximum complement fixation antibody titers posttransplant to cytomegalovirus or herpes simplex virus, type 1. Group A did differ from groups B and C in its frequency of hepatitis, chronic liver disease, episodes of late rejection (greater than or equal to 21 days after transplant), transplant nephrectomy required for rejection, infections whose defense involves intact cell-mediated immunity, and the number of late rejection episodes per patient. Mechanisms underlying these associations are not known but apparently are not related to HLA phenotype.

Iatrogenic arteriovenous fistula. An unusual complication of indwelling pericardial catheter and intrapericardial steroid instillation for the treatment of uremic pericarditis.

The drainage and instillation of poorly absorbable corticosteroids has recently been suggested as an laternative to the present modes of therapy for uremic pericarditis. One patient who underwent such a therapeutic approach subsequently had a left internal mammary artery to right internal mammary vein arteriovenous fistula develop. To our knowledge, this is the first report of the development of arteriovenous fistula after either pericardiocentesis or intrapericardial instillation of steroids.

A longitudinal study of varicella-zoster virus infections in renal transplant recipients.

A serum bank maintained for renal transplant recipients allowed for a longitudinal study of antibody responses before and after herpes zoster. Renal transplant recipients without herpes zoster served as controls. Antibody responses to varicella-zoster virus, herpes simplex virus type 1, and cytomegalovirus were measured. The serological responses following herpes zoster were prompt and sustained (in the majority of cases), transient, or not present at all. Zoster without an eruption occurred (apparent only on retrospective chart review) and furnished an explanation for unexplained unilateral pain syndromes in these patients. Asymptomatic rises in titer of antibody to varicella-zoster virus not explained by rises in antibody to herpes simplex virus occurred in both groups. This latter finding points to an unstable relation between virus and host and supports and hypothesis of Hope-Simpson that subclinical release of virus with resulting antigenic stimulation may maintain immunity to varicella-zoster virus. Patients with herpes zoster and controls did not differ in several humoral immune parameters that might have explained the occurrence of herpes zoster. There was no evidence that herpes zoster precipitated renal graft rejection.