Renal transplants with delayed graft function show decreased renal function despite monitoring with postabsorptive levels

Cyclosporine (CyA) monitoring with postabsorptive levels can predict the risk of an acute rejection episode (ARE). Large doses of CyA are needed to obtain adequate drug exposure. The impact of this strategy on renal function, especially in patients with delayed graft function (DGF), is unknown. We report our experience comparing C3 (3-hour postdose) monitoring with a historical series of cadaveric renal transplants. Sixty-three consecutive patients who received cadaveric renal transplants were followed for 1 year. Group A (historical n = 31) patients received 6 mg/kg/d CyA with the dose adjusted according to the trough level (target, 250-350 ng/mL), group B (study n = 32) received 10 mg/kg/d CyA with dose adjustments based upon C3 (target, 1100-1500 ng/mL). All patients received cyclosporine prednisone and a third agents. The general characteristics of the donors and recipients were comparable. The incidence of biopsy-proven ARE at 1 year in group A was 42% and 19% in group B (P <.05). Patients achieving C3 levels >1000 ng/mL at 1 week displayed significantly lower ARE rates (8% vs 50%; P <.05). The rate of DGF was similar in both groups, but the duration was longer in group B (15 vs 21 days, P <.05). The serum creatinine (SCr) level was significantly higher in group B at 3 months (1.47 mg/dL group A vs 1.76 mg/dL group B; P <.05). Patients in group B with DGF showed significantly higher SCr values at 1 year (1.18mg% vs 2.03 mg%; P <.05). C3 level monitoring of CyA yields excellent results in terms of decreased ARE, but an increased SCR was observed among patients with DGF.     

Renal function and 1 alpha-hydroxyvitamin D3 in rabbits with normal renal function and renal insufficiency

The effect of 1 alpha-hydroxyvitamin D3 (1 alpha OHD3) on the renal clearance of creatinine was investigated in groups of rabbits with stable renal insufficiency and normal controls. Urine was collected in the two groups for two one-week periods during placebo treatment. Then, 1 alpha OHD3, 0.02 micrograms/kg BW/day, was administered orally and urine was collected during the next two weeks. Weekly blood samples were obtained. The treatment had no significant effect on the serum concentrations of calcium and phosphate in either group. Creatinine clearance decreased significantly in both groups during the 1 alpha OHD3 treatment (p less than 0.05), mainly due to a decreased urinary excretion of creatinine. It is suggested that changes in the renal tubular handling of creatinine caused by 1 alpha OHD3 may be the explanation of the observed effect.     

Renal and systemic oxygen consumption in patients with normal and abnormal renal function.

Systemic and renal oxygen consumption and hemodynamics were studied in patients with normal renal function (NI; serum creatinine concentration (Screat), 1.0 +/- 0.04 mg/dL) and those with moderate chronic renal failure with diabetes mellitus Screat, 2.7 +/- 0.2 mg/dL) or without diabetes mellitus (Screat, 2.4 +/- 0.1 mg/dL). Patients with chronic renal failure were anemic and had normal systemic oxygen consumption (NI, 10,564 +/- 277; chronic renal failure, 9,669 +/- 362 mumol of O2/min) and elevated systemic oxygen extraction (NI, 22.9 +/- 1; chronic renal failure, 30.9 +/- 1.2%) (P less than 0.02). Cardiac output and index and arterial oxygen saturation were equivalent in normal patients and in patients with chronic renal failure. Patients with chronic renal failure had higher renal oxygen extraction (NI, 7.3 +/- 0.8; chronic renal failure, 13.9 +/- 1%), lower RBF (NI, 572 +/- 146; chronic renal failure, 197 +/- 20 mL/min/kidney), and lower renal oxygen consumption per kidney (NI, 391 +/- 101; chronic renal failure, 177 +/- 20 mumol of O2/min/kidney) than did normal patients (P less than 0.02). There was a linear relationship between hemoglobin and RBF (r = 0.47, P less than 0.02). Patients with chronic renal failure and diabetes had lower RBF (diabetes mellitus, 146 +/- 23; without diabetes, 242 +/- 28 mL/min/kidney) and renal oxygen consumption per kidney (diabetes mellitus, 131 +/- 21; without diabetes, 218 +/- 29 mumol of O2/min/kidney (P less than 0.03) but equivalent renal oxygen extraction when compared with patients without diabetes. Patients with chronic renal failure without diabetes mellitus had higher renal oxygen consumption when expressed per 100 mL of creatinine clearance (diabetes mellitus, 1,016 +/- 150; without diabetes mellitus, 1,453 +/- 175 mumol of O2/min/100 mL of creatinine clearance; P less than 0.03). There was a significant linear relationship (P less than 0.005, r = 0.38) between calculated creatinine clearance and renal oxygen consumption with a y intercept representing basal renal oxygen consumption (115 mumol of O2/min/kidney) and a slope of 2.3 mumol of O2/mL. Patients with moderate chronic renal failure have normal systemic oxygen consumption but reduced RBF and renal oxygen consumption. The latter parameters are even lower in patients with chronic renal failure and diabetes. Renal hypermetabolism is more likely to exist in nondiabetic than diabetic renal disease. Basic human renal physiology and pathophysiology are described by the relationships between renal oxygen consumption, blood flow, oxygen extraction, and creatinine clearance in patients with normal and abnormal renal function of varied cause.     

Immunotoxins and central nervous system neoplasia.

The poor prognosis associated with central nervous system (CNS) malignancy has led investigators to seek new, innovative treatment modalities. Immunotoxins, carrier molecules linked to toxic agents, combine high specificity for tumor-associated antigens with extreme potency. The rationale for both the development of these compounds and for their application to CNS neoplasia is explained. This report discusses the design and construction of immunoconjugates, using toxins that differ in their mechanism of action bound to ligands directed against various antigens. A comparison is made between the in vitro efficacy of standard chemotherapy and immunotoxins in glioblastoma- and medulloblastoma-derived cell lines. A review is included of the results of experiments in animals with leptomeningeal neoplasia, where prolongation of survival following intrathecal administration of immunotoxins has been reported. The obstacles encountered in clinical trials with other types of cancer are addressed and approaches to optimize the use of these novel agents in the context of treating malignant disease of the CNS are suggested.     

Beta-blockers and the central nervous system.

Some of the interesting points which emerged from an international symposium on beta-blockers and the central nervous system, held in St Moritz in January 1976, are presented. Fifty-eight participants from 12 countries attended the symposium.     

Renal injury in the extremely obese patients with normal renal function

We studied the glomerular architecture in renal biopsies of 95 patients undergoing bariatric surgery for extreme obesity but whose renal function was normal. The comparison group was 40 control patients having protocol biopsies. These latter patients had normal weight and renal function, were non-diabetic, non-hypertensive, and were undergoing nephrectomy or donating a kidney. Logistic regression models determined associations between the clinical and biochemical variables and glomerular lesions. Arterial hypertension, sleep apnea syndrome (SAS), and microalbuminuria were prevalent in the obese patients, as was hyperglycemia to a lesser extent. Focal and segmental glomerulosclerosis was present in only five extremely obese (EO) patients but absent in controls. Increased mesangial matrix, podocyte hypertrophy, mesangial cell proliferation, and glomerulomegaly were more frequent in the obese cohort than in the control group. Body mass index was a significant independent risk factor associated with glomerular lesions in all 135 patients and in the 95 EO patients, whereas SAS was associated with glomerulomegaly only in the EO. Our study shows that EO patients who lack overt clinical renal symptoms have a variety of glomerular abnormalities that correlate with body mass.     

Melanoma of the central nervous system.

The neurological manifestations of melanoma are analysed in this review of 1,500 patients in the Queensland Melanoma Project from 1963 to 1969. Three hundred and fifty patients have died, and 113 were recognized as having central nervous system metastases. The natural history of these metastases was examined, together with the results of a limited number of autopsies. The results of treatment are discussed.     

Renal handling of urea in subjects with persistent azotemia and normal renal function

Fourteen subjects with persistent azotemia and normal glomerular filtration rate were studied by renal clearances and hormonal determinations to establish the nephron site of altered urea transport and the mechanism(s) responsible for their azotemia. During constant alimentary protein, urea nitrogen appearance was normal and urea clearance was much lower than in 10 age-matched control subjects (23.3 +/- 2.1 ml/min and 49.6 +/- 2.6 ml/min per 1.73 m2, P less than 0.001). Inulin and para-aminohippurate clearances, blood volume and plasma concentration of antidiuretic hormone were within normal limits. During maximal antidiuresis, in spite of greater urea filtered load, the urinary excretion of urea was less, and both the maximum urinary osmolality and the free-water reabsorption relative to osmolar clearance per unit of GFR were greater than in control subjects. After sustained water diuresis, the plasma urea concentration markedly decreased to near normal levels in azotemic subjects. The basal urinary excretion of prostaglandins E2 was significantly reduced in azotemic subjects and was directly correlated with fractional urea clearance (r = 0.857, P less than 0.001). An additional group of control subjects (N = 8) showed a marked reduction of fractional clearance of urea after inhibition of prostaglandin synthesis (P less than 0.01). These data suggest that azotemia is due to increased tubular reabsorption of urea in the distal part of nephron, presumably because of increased back diffusion in the papillary collecting duct, accounting for the enhanced maximum urinary osmolality and free-water reabsorption. Renal prostaglandin E2 may participate in the pathogenesis of azotemia by altering recycling of urea in the medulla.     

Renal revascularization to preserve and restore renal function.

A total of 97 patients underwent 107 renal revascularization procedures for restoration and preservation of renal function. Of the 4 groups of high risk surgical patients that emerged an overall successful outcome was achieved in 83%, with a 6% mortality rate and an 11% morbidity rate. Renal revascularization for restoration and preservation of renal function can be performed safely with good results. The preoperative serum creatinine level was not predictive of the surgical outcome. Alternative bypass procedures are preferred.     

Neurofibromatosis and central nervous system tumors in childhood.

Neurofibromatosis is a multifaceted disease that often results in tumors of the central nervous system. As our understanding of the molecular biology of the disease improves along with better neuroradiology imaging, surgical instrumentation, and adjunctive care, the management schemes for these patients are evolving. This article reviews what is known about neurofibromatosis, common management problems with respect to the central nervous system, and an approach to the handling of these issues.     

Fatal central nervous system infection with varicella-zoster virus in renal transplant recipients

Three renal transplant patients with culture-positive central nervous system infections resulting from varicella-zoster virus died of the virus infection. No finding predicting a poor outcome in these patients could be identified. Varicella-zoster infection in transplant recipients is a potentially fatal disease, and upon diagnosis should it be treated by (1) reduction in immunosuppression, and (2) initiation of either vidarabine or acyclovir as specific antiviral therapy.     

Superficial siderosis of the central nervous system: secondary progression despite successful surgical treatment, mimicking amyotrophic lateral sclerosis. Case report and review

Superficial siderosis of the central nervous system is a rare disorder with hemosiderin deposition in the spinal and cranial leptomeninges and subpial layer, mostly from repetitive subarachnoid hemorrhage. Progressive sensorineural deafness, cerebellar ataxia, and pyramidal signs comprise the typical clinical presentation. We describe a 47-year-old patient, who showed initial 2-year improvement after successful occlusion of an intradural bleeding source at T4. Secondary progression of symptoms without further bleedings was noted thereafter, with a clinical picture of amyotrophic lateral sclerosis. This case illustrates that the disease may progress secondarily even without re-bleedings, and that secondary progression might be due to a similar pathomechanism as in amyotrophic lateral sclerosis.     

Primary central nervous system lymphoma with paraproteinemia.

BACKGROUND: Although 34% to 54% of cases of extraneural non-Hodgkin's lymphoma (NHL) of the B-cell type are associated with monoclonal paraproteinemia, primary central nervous system NHL (PCNSL) with paraproteinemia has rarely been reported. The authors present herein a case of PCNSL with monoclonal immunoglobulin M (IgM) paraproteinemia. METHODS AND RESULTS: A 78-year-old woman was referred to our hospital because of hemiparesis and epilepsy. Magnetic resonance imaging showed a round mass in the left frontal region. Serum IgM was 3,820 mg/dL, and immunofixation revealed an IgM kappa monoclonal paraprotein. No lymphoplasmacytic infiltration was observed on bone marrow aspiration. The brain tumor was totally resected. The pathological diagnosis was NHL (diffuse, large B cell). The results of immunohistochemical staining for IgM were strongly positive in the tumor cells. CONCLUSION: This type of PCNSL has rarely been reported and little is known about it. It is possible that the true incidence of paraproteinemia caused by PCNSL is higher than has been thought. The clinical features of the tumor and pertinent literature are reviewed.     

Infective agents in the central nervous system.

Almost all agents can cause infection within the central nervous system. The extent of infection ranges from diffuse involvement of the meninges, brain, or spinal cord to localized involvement presenting as a space-occupying lesion. Epidemiologic considerations, appreciation of the presenting clinical syndrome (acute bacterial meningitis, acute aseptic meningitis, chronic meningitis, or space-occupying lesion), and cerebrospinal fluid analysis facilitate arrival at a diagnosis.