Primary care of patients with renal transplants

The number of renal transplant recipients in the community continues to rise due to improved organ and patient survival. With increasing emphasis on primary care, more organ transplant recipients are being cared for by primary care physicians. This article outlines the management of renal transplant recipients and reviews the problems unique to this group of patients.     

Quantitative evaluation of renal parenchymal mass with 99mtechnetium dimercapto-succinic acid scintigraphy after nephrolithotomy

PURPOSE: We detected renal parenchymal damage after nephrolithotomy. MATERIALS AND METHODS: We studied 12 patients with renal stones treated with nephrolithotomy. Renal function was determined with serum blood urea nitrogen (BUN) and creatinine values, and 99mtechnetium dimercapto-succinic acid scintigraphy of renal parenchymal tissue was performed before, and 7 days and 3 months after nephrolithotomy. Qualitative and quantitative analyses were done with the Wilcoxon signed rank test. RESULTS: There was no visual difference in size and appearance of the nephrotomy site between preoperative and postoperative visual scintigraphic evaluations. Quantitative data did not reveal any significant difference between kidneys with and without a nephrotomy incision (p > 0.05), as well as between nephrotomy regions and intact parenchyma within the same kidney (p > 0.05) 3 months after nephrolithotomy. There was no significant difference in serum BUN and creatinine levels between values preoperatively and 3 months postoperatively (p > 0.05). CONCLUSIONS: There was no significant change in renal cortical function and functioning renal parenchymal mass after nephrolithotomy as shown by serum BUN and creatinine levels, and 99mtechnetium dimercapto-succinic acid scintigraphy.     

Primate renal transplants using immunotoxin

BACKGROUND: T-lymphocyte depletion 7 days before transplantation with immunotoxin FN 18-CRM9 has resulted in tolerance to subsequent renal allografts. We tested the effect of giving immunotoxin on the day of the transplantation and evaluated its effect on rhesus monkey and allograft survival, on antibody production, and on T-cell recovery. METHODS: Major histocompatibility complex mismatched renal allografts were performed in rhesus monkeys. Immunotoxin was given starting on the day of transplantation, with and without prednisone and mycophenolate mofetil for 3 days. T-cell subsets and alloantibody levels were measured by flow cytometry. The ability of treated monkeys to develop antibody to tetanus, diphtheria, and xenoantibody was measured. Histology of renal transplants was read in a blinded manner. RESULTS: Immunotoxin started on the day of transplantation resulted in prolonged allograft survival in all treatment groups. Graft loss between days 50 and 135 was most often due to interstitial nephritis. Later graft loss was due to chronic rejection. Monkeys had intact antibody responses to alloantigen, tetanus, diphtheria, and xenoantibody. Their CD4 cells recovered gradually over 6 months. CONCLUSIONS: Immunotoxin reliably prolongs renal allograft survival when started on the day of transplantation, but interstitial nephritis and chronic rejection limit the development of long-term tolerance. T-cell-dependent B-cell responses remain intact after treatment.     

Long-term evaluation with DMSA-Tc 99m scintigraphy of renal parenchymal involvement in children after shockwave extracorporeal lithotripsy

BACKGROUND: Endothelin 1 (ET-1), a vasoconstrictor peptide, has been implicated as a tumour growth stimulator and an angiogenesis factor. METHODS: To assess the involvement of ET-1 in colorectal cancer, immunoelectron microscopy for ET-1 was performed in colorectal liver metastases and normal liver (n = 6). ET-1 plasma levels were measured by radioimmunoassay in patients with colorectal cancer, with (n = 18) and without (n = 12) liver metastases, and in controls (n = 22). RESULTS: In normal liver, ET-1 was present in endothelial cells; in tumour, it was observed in endothelial cells, tumour cells and myofibroblasts. Mean(s.d.) plasma ET-1 levels were 2.75 (1.37) pg/ml in controls, 4.53(1.61) pg/ml in patients with colorectal liver metastases (P = 0.001) and 3.92(1.32) pg/ml in patients without metastases (P = 0.02). CONCLUSION: ET-1 was present in various cell types within colorectal liver metastases and raised levels were found in the plasma of patients with colorectal cancer. ET-1 may not only modulate tumour vascular tone but also act on tumour growth and angiogenesis, both locally and systemically.     

Acute renal insufficiency in renal transplants treated with interferon-alpha for chronic hepatitis C

Small-angle x-ray scattering (SAXS) can provide information on mean size, predominant orientation and typical shape of mineral crystals in bone. In this paper, recent developments of this technique for application in bone research are reviewed. Then the structure of the collagen/mineral composite in bone, as determined by SAXS, is compared for a number of species. The thickness of the mineral crystals was found to increase with age up to a value around 3 to 4 nanometers in adult animals, depending on the species. The SAXS results also suggest the existence of needle-shaped mineral crystals in mouse or rat bone and more plate-shaped crystals in other tissues like adult human bone or mineralized turkey leg tendon.     

Captopril renal scintigraphy in renovascular hypertension

Renovascular disease is a common cause of secondary hypertension. Renal artery stenosis is present in up to one third of patients with clinical markers suggestive of renovascular hypertension, such as hypertension refractory to medical management, severe hypertension in a young patient and worsening of renal function after the use of an angiotensin-converting enzyme inhibitor. Early discovery of renal artery stenosis may allow amelioration or cure of the hypertension and halt progressive loss of renal function. Although renal arteriography remains the gold-standard aid to diagnosis and to planning surgical intervention, it is an invasive procedure that may cause deterioration of renal function. In the presence of renal artery stenosis, glomerular filtration is maintained by angiotensin. Administration of captopril in renal scintigraphy removes this compensatory mechanism and causes a temporary impairment of renal function in the affected kidney. Nuclear tracers can visualize this impairment, thus allowing assessment of the physiologic significance of a renal artery stenosis. The test can be done as a outpatient procedure.     

Renovascular hypertension and captopril-enhanced renal scintigraphy

Renovascular hypertension (RVH) is a secondary hypertension that is caused by the renal artery stenosis and is curable by surgical treatment. Sensitivity and specificity of CRS for RVH have been reported to be in exceed of 90%. Captopril-enhanced renal scintigraphy (CRS) has become an important tool in the diagnosis of RVH. In addition, the recent reports indicate that CRS is a promising means of prognostic evaluation in re-vascularization of RVH. In this report, pathophysiological considerations, methods, diagnostic criteria, diagnostic efficacy and consideration for clinical application are reviewed.     

Functional and morphologic studies on allogeneic venous transplants

Erythropoietin production was studied in 30-day-old and adult rats previously injected with pharmacological doses of isoproterenol. The animals were stimulated either by hypobaric hypoxia or by a combination of hypoxia and acute anemia. The erythropoietic activity of the plasma was measured by 59Fe incorporation in total circulating red blood cells of mice made polycythemic by chronic hypoxia. The results were converted to units of erythropoietin (IRP). A significant reduction of erythropoietin production was observed only in young rats. Our interpretation of the findings is that isoproterenol induced the differentiation of the salivary glands in the young animals hence reducing hormone production at the extrarenal (submandibular) level.     

Torsion of intraperitoneal renal transplants: imaging appearances

OBJECTIVE: Torsion of a renal transplant is a rare complication with nonspecific clinical manifestations. Prompt detection is necessary to allow surgical treatment and to preserve renal function. We describe the radiologic appearances of torsion of intraperitoneal renal transplants in patients who have undergone simultaneous renal and pancreatic transplantation or dual renal transplantation. CONCLUSION: Renal transplant torsion should be suspected when a change in renal axis associated with abnormal perfusion occurs in an intraperitoneal kidney.     

The value of renal scintigraphy during controlled diuresis in children with hydronephrosis

The mutation of serine128 to arginine in the CD 62E gene is a risk factor for coronary artery disease (CAD). We designed a new method to detect this mutation based on the observation that it is due to a transversion of nucleotide A561 to C, which abolishes a PstI recognition site. Two alleles, A and C, are easily typed when genomic DNA is amplified by PCR, digested with PstI, and separated on agarose gels. Among 153 people who underwent an elective, diagnostic arteriography in Johns Hopkins Hospital, we found that the C allele accounts for 19.5% in angiographically documented CAD patients (n = 82). It is significantly higher than the 10.6% frequency observed in normal controls (n = 71, p < 0.05). It indicates that the C allele is associated with early-onset CAD. This new method should facilitate the screening of this mutant allele in large populations and contribute to the understanding of the molecular mechanism underlying the association of this mutation with CAD.     

Diltiazem disposition and metabolism in recipients of renal transplants

Owing to increasing evidence showing the importance of lipid peroxidation in oxidative stress in vivo, the role and evaluation of antioxidants have received much attention. Ginkgo biloba extract (GBE), well-known as an efficient drug against diseases induced by free radicals, has been suggested to exert its effect by antioxidant action. A method was established to determine the activity of GBE as a hydrogen donor by stoichiometric and kinetic studies, and GBE was compared with several other antioxidants such as alpha-tocopherol, propyl gallate, and two kinds of flavonoids which are found in GBE, quercetin, and kaempferol. It was found that there were 6.62 x 10(19) active hydrogens in 1 g of GBE. Stoichiometric studies showed that one molecule of alpha-tocopherol reacted with one molecule of galvinoxyl radical. For quercetin, kaempferol and propyl gallate, the experimental stoichiometric numbers were 4.0, 1.9, and 3.1, respectively. The rates of reaction of antioxidants with galvinoxyl in ethanol were determined spectrophotometrically, using a stopped-flow technique. The second-order rate constant, k2, obtained at 25 degrees C was 0.13 (g/L)(-1)s(-1) for GBE and 5.9 x 10(3), 2.1 x 10(3), 1.2 x 10(4), and 2.4 x 10(3) M(-1)s(-1) for quercetin, kaempferol, propyl gallate, and alpha-tocopherol, respectively. The second-order rate constant, k2', on the molar basis of active hydroxyl groups in the tested substances obtained at 25 degrees C decreased in the order of propyl gallate > alpha-tocopherol > quercetin > GBE approximately kaempferol. This is the first study on GBE as an antioxidant which reports both stoichiometric and kinetic results.     

Converting-enzyme inhibitor versus calcium antagonist in cyclosporine-treated renal transplants

The influence of antihypertensive treatment on the long-term evolution of arterial pressure and renal function was studied in a prospective controlled trial conducted in renal transplant recipients treated by cyclosporine. Within six months after transplantation, patients were randomly allocated to treatment by the angiotensin-converting enzyme inhibitor, lisinopril (ACEI, alone or associated with frusemide; N = 14), or the calcium antagonist, nifedipine (CA, alone or associated with atenolol; N = 11). Glomerular filtration rate (TcDTPA clearance) and effective renal plasma flow (hippuran clearance) as well as 24-hour urinary excretion of electrolytes and albumin were estimated at about 1 and 2.5 years of follow-up. Before initiation of antihypertensive therapy, the two groups were similar with regards to mean arterial pressure (119 +/- 2 vs. 120 +/- 4 mm Hg), effective renal plasma flow (285 +/- 26 vs. 248 +/- 33 ml/min/1.73 m2) and glomerular filtration rate (59 +/- 4 vs. 61 +/- 8 ml/min/1.73 m2 in the ACEI and CA groups, respectively). Both ACEI and CA treatments were associated with no change in renal function, a similar change in mean arterial pressure (ACEI -18 +/- 3; CA -13 +/- 5 mm Hg) and identical trough blood levels of cyclosporine. Urinary albumin excretion did not change significantly in any groups. Of interest, only in the ACEI group did filtration fraction significantly decrease (from 0.22 +/- 0.01% to 0.19 +/- 0.01% at final studies). These results indicate that in cyclosporine-treated transplant recipients, a satisfactory control of hypertension is obtained by chronic ACEI, which is as effective on arterial pressure as a combination of CA and atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bronchiolitis obliterans after bone marrow transplantation: evaluation with lung scintigraphy

Hypophosphatasia is a rare disorder characterised by low levels of serum alkaline phosphatase activity resulting in abnormal phosphorylated metabolites and varying skeletal abnormality. We have followed a patient with adult type hypophosphatasia for over ten years who has also shown a persistently elevated tartrate resistant acid phosphatase activity (TRAP) without any obvious cause. Characterisation of this TRAP by polyacrylamide gel electrophoresis (pH 4.0) showed migration to band 5 position. Molecular weight determination by FPLC and an estimate of the molecular weight by gradient gel electrophoresis gave a molecular weight of 29,000-43,600. This molecular weight makes it unlikely for this to be a IgG/TRAP complex persisting in the circulation. Paranitrophenylphosphate was the preferred substrate. This characterises the enzyme as type 5 acid phosphatase which is of the mononuclear/phagocyte type, possibility of osteoclastic origin, though the tissue source remains unknown.     

Tc-99m DTPA perfusion scintigraphy and color coded duplex sonography in the evaluation of minimal renal allograft perfusion

During the past two years, a growing number of mutations have been identified in three of the four members of the fibroblast growth factor receptor (FGFR) family as causing autosomal dominant disorders of skeletal and cranial development. These mutations map to the extracellular domain, the transmembrane domain, or the tyrosine kinase domain of these receptors. Recent studies demonstrate that a common mechanism, constitutive activation of receptors signaling, underlies most, if not all, of these disorders. This suggests a normal role for FGFRs in the negative regulation of bone growth.     

Serial renal transplant surgery: technical reflections concerning third transplants

Iodine distribution was studied in isolated porcine eyes after iontophoresis using 131I-labelled solutions and chemical methods. After a 15-min treatment with a therapeutically used iodine brine, the iodine content in the ocular tissues showed the following rank order: cornea > retina > vitreous body > anterior chamber fluid > lens. Replacement of the brine by 0.15 M NaI increased the uptake values in a different way, but the same rank order was maintained. The increase was highest in the cornea (5.6-fold) and only about 2-fold in the lens, nevertheless approaching now the level of 10(-4) M, a concentration which was regarded as being optimal for the antioxidant effect of I-. Among the other eye components, the relatively high iodine enrichment of the retina was remarkable. The data are discussed with respect to a possible protective, antioxidative and OH-scavenging efficacy of I- and to previous results in the literature concerning iodine uptake in ocular tissues.     

Pentavalent technetium-99m-dimercaptosuccinic acid scintigraphy in renal osteodystrophy

OBJECTIVE: To establish whether oxytocin modifies the stimulatory effect of vasoactive intestinal polypeptide (VIP) on prolactin secretion in healthy women. DESIGN: Controlled clinical study. SETTING: Healthy women in an academic research environment. PATIENT(S): Seven healthy women (aged 24-32 years) were tested on the 22nd day of two consecutive normal menstrual cycles. INTERVENTION(S): Vasoactive intestinal polypeptide (4 pmol x kg(-1) x min(-1) in 50 mL of normal saline infused i.v. for 60 minutes) was administered in either the presence or absence of concurrent treatment with oxytocin (2 IU injected plus 0.07 IU/min infused for 60 minutes). MAIN OUTCOME MEASURE(S): Serum prolactin levels. RESULT(S): The administration of VIP induced a significant increase in serum prolactin levels, with a mean peak response 1.6 times higher than baseline at 45 minutes after injection. In the presence of oxytocin, the prolactin response to VIP was significantly higher, with a mean peak response 2 times higher than baseline. CONCLUSION(S): These data suggest that in healthy women, oxytocin facilitates the regulation of the stimulating effect of VIP on prolactin secretion.     

Technetium-99m dimercaptosuccinic acid scintigraphy studies of renal cortical scarring and renal length

The aims of this study were to validate 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy appearances with histopathological features of scarring; to evaluate the sensitivity and specificity of 99mTc-DMSA and ultrasound for the detection of renal scarring; to compare planar, pinhole and SPECT techniques when using 99mTc-DMSA; and to compare 99mTc-DMSA and ultrasound renal length measurement. METHODS: Reflux nephropathy was induced in large white pigs using established methods. To ensure that the abnormalities detected were scars and not inflammatory changes, the pigs were not studied until 3 mo after the treated episode of acute pyelonephritis confirmed by 99mTc-DMSA. RESULTS: Twenty pigs were enrolled in the study. Eleven reached the end point, but only nine pigs (18 kidneys) were available for analysis. Thirty-four scars were identified pathologically; 24 were present macroscopically and a further 10 were seen only on microscopy. Technetium-99m-DMSA abnormalities correlated with scars histopathologically with an accuracy of 92% versus that of ultrasound, 75% (p < 0.001). Technetium-99m-DMSA more accurately identified scarring with a higher sensitivity (76% versus 29%) and specificity (98% versus 92%) than ultrasound. On the 99mTc-DMSA study, pinhole imaging had the highest accuracy (92%) when compared with planar (90%) and SPECT (87%) data. These differences were not statistically significant. Renal lengths as measured on 99mTc-DMSA more closely correlated with length measurement at pathological examination than ultrasound. Technetium-99m-DMSA measurement was, on average, 6% higher than pathology, and ultrasound was, on average, 22% lower. CONCLUSION: Technetium-99m-DMSA appears to be the preferred method for the detection of renal cortical scarring and accurate renal length measurement when compared with ultrasound examination.