Mycobacterial infection after renal transplantation--report of 14 cases and review of the literature.

During a nine-year period, 14 cases of mycobacterial infection (tuberculosis) developed in 403 renal transplant recipients at the King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia, an incidence of 3.5 per cent. The annual incidence of tuberculosis was about 50 times higher than that in the general population. Infection was disseminated in nine (64.3 per cent), pulmonary in four (28.6 per cent), and genitourinary in 1 (7.1 per cent). In one patient tuberculosis was transmitted by the donor's kidney. The clinical manifestations were often ill-defined and not different from that in the normal host. Cultures from all patients grew Mycobacterium tuberculosis; concomitant infection with other organisms was present in five patients (35.7 per cent). Two of 18 patients (group 1) with positive pretransplant tuberculin skin test developed tuberculosis after transplantation (11 per cent), and neither received isoniazid prophylaxis; three of 70 patients (group 2) with negative skin tests developed tuberculosis after transplantation (4.3 per cent). The difference between the two groups was not statistically significant. Review of all published cases of mycobacterial infections in renal transplant recipients revealed 130 cases. Tuberculosis was disseminated in 38.7 per cent, pulmonary in 40.2 per cent, cutaneous in 12 per cent, and miscellaneous in 9.4 per cent. Atypical mycobacteria were responsible for 29 per cent of disseminated infections, 8 per cent of pulmonary infections and all cases of cutaneous and articular tuberculosis. Invasive procedures were needed to establish the diagnosis in 21 of 33 disseminated cases but in only three of 47 cases of pulmonary tuberculosis (p less than 0.0001). The mortality rate from disseminated disease was 37 per cent and from all other forms of tuberculosis was 11 per cent (p less than 0.005). These findings (1) confirm the higher incidence of tuberculosis in renal transplant recipients, compared to the general population; (2) suggest that pretransplant skin testing probably has little value in identifying patients at risk; (3) show that disseminated tuberculosis is common after renal transplantation and requires invasive procedures for diagnosis; (4) confirm that the donor kidney may be an important source of infection; and (5) indicate that concomitant infection with other organisms is common.

Kaposi's sarcoma: the most common tumor after renal transplantation in Saudi Arabia.

Between September 1975 and November 1986, 263 renal transplant recipients at the King Faisal Specialist Hospital and Research Center were followed; 82 procedures were done by the authors using live related donors. Among the 263 patients, 14 cases of Kaposi's sarcoma were identified, an incidence of 5.3 percent compared with an incidence of 0.4 percent in renal transplant recipients from Western countries. In addition, two more patients had other types of tumors. Thus, Kaposi's sarcoma represents 87.5 percent of tumors in the King Faisal Hospital renal transplant population, in contrast to 3.7 percent in the Cincinnati Transplant Tumor Registry. The mean period between transplantation and diagnosis of Kaposi's sarcoma was 12.5 months (range, one to 37 months). Eleven patients were Saudis and three were other Arab nationals. Seven of the 11 Saudi patients were from the southwestern region of the country. Cytomegalovirus titers were not elevated in six of 10 patients. Results of tests for human immunodeficiency virus were negative in seven of eight patients. HLA-A2 antigen frequency was significantly increased in the King Faisal Hospital renal transplant patients with Kaposi's sarcoma as compared with a control population (83.3 percent versus 43.6 percent, p value = 0.006 [P = 0.06 with Bonferroni adjustment]), and increased, though nonsignificantly, compared with the live related kidney transplant recipients without Kaposi's sarcoma (83.3 percent versus 49.4 percent, p value = 0.058 [P = 0.58 with Bonferroni adjustment]), suggesting a genetic predisposition to Kaposi's sarcoma in these patients.

Assessing the adequacy of dialysis.

In previous work, probes of brain function (quantified EEG and cognitive performance) objectively measured clinical differences patients with chronic renal failure before and after treatment with maintenance haemodialysis or transplantation. This study applied those measures (EEG-discriminant score; choice reaction time, CRT; continuous memory test, CMT; clinical-symptom/self-evaluation questionnaire, CSE) in a prospective experiment to determine whether our standard amount (time) of thrice weekly dialysis could be reduced without inducing some degree of clinical uraemia. In 10 patients a 6 month experimental (E) period was preceded by a 3 month control (CI) and followed by a 3--6 month control (C2) period. During E dialysis time was reduced so that residual renal (Kr) plus dialyser (Kd) urea clearance per week per litre of patients' body water approximated 50--80 percent of the control-level of 3000ml/wk/L. In response average values of all measures worsened; EEG, 54 percent; CRT, 2.5 percent; CMT, 21 percent; and CSE, 11 percent. BUN levels rose slightly, urea generation rates fell, and patients insisted that they felt better as they recorded more severe symptoms (CSE). We conclude: (i) that Kr + Kd = 3000ml/wk/L approximates a minimum level of adequate dialysis; (ii) objective measures which index the neurobehavioural syndrome of clinical uraemia detect inadequate (reduced) dialysis.

Hemodialysis and renal transplantation in progressive systemic sclerosis: report of 2 cases.

Renal failure is a common cause of death in patients with progressive systemic sclerosis (PSS). The present paper describes two patients with chronic renal failure secondary to PSS whom we have treated by a combination of chronic hemodialysis and renal transplantation. Also reviewed are reports of six additional patients who have undergone renal transplantation. We conclude that chronic hemodialysis and renal transplantation are successful life-sustaining treatment modalities in some patients with end-stage renal disease due to PSS.

Quantitative indices of clinical uremia.

The disabling, dialysis-responsive symptoms of clinical uremia primarily represent impaired functions of the nervous system. Accordingly, these studies used several quantitative electrophysiologic and cognition-dependent probes of nervous system function: peripheral nerve-conduction velocity, response latency and amplitude; electroencephalographic (EEG) power-spectrum analysis; visual evoked response latency; EEG responses to photic driving; and measures of integrated behavioral performance that stressed sustained and selective attention, reaction time, speed of decision-making, short-term memory, and mental manipulation of symbols. Probes of quanitified central nervous system function consistently revealed impairments that varied directly with the degree of renal failure, that improved following onset of maintenance dialysis, and that improved still further after successful renal transplantation. In contrast, measures of peripheral nerve function were generally unchanged. Neurobehavioral measures that are relevant to uremic symptomatology provide quantitative estimates of the clinically significant, whole-organism biologic effects of renal failure and its several treatments. Applications of such measures in studies of symptomatic states other than uremia are indicated also.

Toxicity of aliphatic amines in uremia.

Fifty-three samples in 26 patients were analyzed for aliphatic amines (DMA and TMA), and the levels correlated with 2 neurophysiological tests, choice reaction time (CRT), and electroencephalogram (EEG). A significant correlation was found between TMA and CRT and EEG (p less than 0.001 and 0.003, respectively) and between DMA and CRT (p less than 0.01). These amines reflect part of the spectrum of toxic compounds which accumulate in uremia. Dissociation of neurophysiological functions may be helpful in evaluating various classes of potentially toxic compounds found in renal failure, as exemplified by short-chain aliphatic amines.

Carbon tetrachloride toxicity potentiated by isopropyl alcohol. Investigation of an industrial outbreak.

Fourteen workers in an isopropyl alcohol packaging plant became ill after accidental exposure to carbon tetrachloride. In four, renal failure or hepatitis developed. Isopropyl alcohol potentiation of carbon tetrachloride toxicity has been shown previously only in rats. Acetone, a product of isopropyl alcohol metabolism, is a major potentiator of carbon tetrachloride toxicity. Workers had elevated levels of acetone in samples of expired alveolar gas and thus were metabolically predisposed to carbon tetrachloride injury. Stricter limits for industrial carbon tetrachloride exposure should be established where concomitant isopropyl alcohol use occurs.

Long-term hemodialysis for patients over 50.

Hemodialysis can hodl end-state renal failure at bay and enable patients to lead a relatively normal life-regardless of their age. In a 10 year retrospective study of 574 patients, the 154 patients over 50 had about the same survival rates as younger persons for the first three years of dialysis. After that, the older patients had higher mortality. Patients who dialyzed themselves at home-with a relative or friend to help-had much better results than those who were dialyzed at the center. This in part reflects the selection process, since patients with severe medical problems usually weren't allowed to try self-dialysis. Older patients did particularly well on home dialysis, which was attributed to their maturity and dependability. Older patients with cardiac instability may require carefully monitored dialysis at the center and frequent blood transfusions. In general, though, patients over 50 needed fewer transfusions and fewer days in the hospital than younger patients.

Quantitative assessment of the electroencephalogram in renal disease.

EEGs wre recorded from renal patients to determine if there are quantifiable characteristic changes in the EEG was quantified by calculating the percentage of spectral power in the bandwidth 3-7 c/sec referrred to a frequency range of 3-13 c/sec and by computing the mean frequency of the dominant rhythm in the EEG. Blood urea nitrogen and creatinine concentrations, as well as a self-assessment of the patient's clinical condition, were recorded. The general finding of this research is that EEG slowing, as evaluated by power spectral techniques, is correlated with uremia-associated variables. 1. In a non-dialyzed patient population with renal failure, slowing in the EEG was found to be directly corelated with increased creatinine concentrations. 2. Quantitative measures of slow wave activity computed using power spectral techniques were found to be highly corelated with an estimate of slowing made by an electroencephalographer. 3. Compared with undialyzed azotemic patients, malignant hypertensive patients with comparable serum creatinine concentrations typically displayed increased slow wave activity, while slowing was generally reduced in the dialyzed patient population. 4. A series of EEGs recorded from one patient during the first three dialyses of her life revealed that slow wave activity decreased during each successive dialysis. In another patient, all quantified EEG values recorded prior to renal transplantation significantly improved after transplantation...

Studies of the elevated extracellular concentration of cyclic AMP in uremic man.

This study was designed to elucidate the mechanism of elevation of plasma cyclic AMP in uremic man. Plasma cyclic AMP was measured in 15 normal subjects and in 18 patients with severe renal failure. In some members from both groups the kinetic parameters of the metabolism of extracellular cyclic AMP were measured. Plasma cyclic AMP was elevated from 23 nM in control subjects to 59 nM in uremic patients, regardless of the presence or absence of the kidneys or parathyroid glands. A single pass of uremic blood through a Kiil hemodialyzer decreased plasma cyclic AMP from 58 to 30 nM. The clearance of cyclic AMP by the dialyzer correlated directly with the blood flow passing through the machine. Hemodialysis for 6 h decreased plasma cyclic AMP levels in the systemic circulation by only 12%. Studies with tritiated cyclic AMP revealed a plasma clearance rate of 624 ml/min in normal subjects and of 344 ml/min in patients with uremia. Such a large decrease in plasma clearance rate cannot be explained by a failure of urinary excretion of cyclic AMP and suggests impairment of "metabolic clearance." In addition, the "plasms production rate" of cyclic AMP was 65% higher in patients with renal failure than in normal subjects. It is concluded that the elevation of plasma cyclic AMP in uremic man is due to a combination of: (a) lack of urinary excretion, (b) decreases metabolic clearance, and (c) increased production of plasma cyclic AMP.

Neurotoxicity in uremia.

The dialysis patient is aware that his behavior evokes reciprocal and complicating responses from important people in his environment. These interactions are perceived and conducted by neurochemical mechanisms which may be impaired in the abnormal chemical environment imposed in renal failure. It is the behaviors we comprehend as indicators of disordered nervous mechanisms. Therefore, it is logical that neurophysiological and neurobehavioral phenomena should be measured quantitatively in order 1) to estimate objectively the patients' success in achieving the goal of maintenance dialysis treatment, 2) to assess the comparative adequacy of dialysis regimens and 3) to provide objective endpoint measures which are relevant to uremia for further investigations of the etiology and pathogenesis of these critically significant uremic manifestations. Our experimental results illustrate that: 1) measures of conduction velocity, distal latency and response amplitudes, as employed by us, were relatively insensitive in the patients and circumstances studied; 2) several neurophysiological measures, i.e., the spontaneous EEG, VER latency and, perhaps, photic stimulation, on the other hand, are highly correlated with the severity of renal failure; 3) behavioral measures of sustained attention and alertness (TMT), of short-term memory (ASTM) and of cognitive manipulation of symbols (AR) are also highly correlated with the severity of renal failure; 4) some measured abnormalities improve following dialysis, but not always to normal--three residual impairments may indicate dialysis in adequacy; 5) several of these measures can provide objective evidence for adequacy of dialysis and other clinical and treatment effects in patients with renal failure.

Neurobehavioral dysfunction in uremia.

To summarize our concepts relating to impaired function of the mind in uremic patients before and during treatment with maintenance dialysis, the emphasis had gradually shifted from the use of "static taxonomy", the diagnostic labels of mental illness, to a more dynamic and sympathetic appreciation that the observed behaviors represent patients' attempts to cope with disease and threats of disability and death, as influenced by varying levels of intelligence, education, cultural conditioning, life experiences and organization of personality defense mechanisms. The dialysis patient is aware that his behavior evokes reciprocal and complicating responses from important people in his environment. These interactions are perceived and conducted by neurochemical mechanisms of the brain which may be impaired in the abnormal chemical environment imposed by renal failure. It is the behaviors we perceive as indicators of disordered nervous mechanisms. Therefore, it is logical that neurobehavioral phenomena should be measured quantitatively in order 1) to estimate objectively the patients' success in achieving the goal of maintenance dialysis treatment, 2) to assess the comparative adequacy of dialysis regimens and 3) to provide objective end-point measures which are relevant to uremia for further investigations of the etiology and pathogenesis of these critically significant uremic manifestations. Our experimental results using ipsitive cognition performance tasks clearly suggest that discrete human performances may be evoked and employed to detect mentational impairments of uremia in quantitative terms, a fundamental step having central relevance to what dialysis does in controlling uremic symptoms.

Primary renal candidiasis with renal granulomata and salt-losing nephropathy.

A patient is reported whose illness was characterized by chronic renal failure associated with persistent salt-wasting, chronic nephrolithiasis, and candiduria which was documented to be arising from the upper urinary tract. Intravenous amphotericin B was effective in eradicating candiduria. However, bilateral nephrectomy was ultimately performed which revealed extensive involvement of the renal parenchyma with classic caseating granulomas apparently related to renal candidiasis. Severe medullary erosion and tissue loss existed which appeared to result in disproportionate medullary destruction which was probably the most significant factor in explaining the patient's salt-losing state. The patient has since been satisfactorily managed with maintenance hemodialysis.