Treatment of vitamin D deficiency in CKD patients with ergocalciferol: are current K/DOQI treatment guidelines adequate?

BACKGROUND: Vitamin D deficiency/insufficiency (VDDI) is common in CKD patients and may be associated with abnormal mineral metabolism. It is not clear whether the K/DOQI recommended doses of ergocalciferol are adequate for correction of VDDI and hyperparathyroidism. METHODS: Retrospective study of 88 patients with CKD Stages 1 - 5 and baseline 25-hydroxyvitamin D level < 30 ng/ml (< 75 nmol/l). Patients treated with ergocalciferol as recommended by K/DOQI guidelines. Only 53 patients had elevated baseline PTH level for the CKD stage. Patients were excluded if they received vitamin D preparations other than ergocalciferol or phosphate binders. 25-hydroxyvitamin D level, intact PTH level (iPTH), and other parameters of mineral metabolism were measured at baseline and after completion of ergocalciferol course. RESULTS: 88 patients with CKD were treated with ergocalciferol. Mean age 56.8 +/- 9.5 years and 41% were males. The mean (+/- SD) GFR was 28.3 +/- 16.6 ml/min. At the end of the 6-month period of ergocalciferol treatment, the mean 25-hydroxyvitamin D level increased from 15.1 +/- 5.8 to 23.3 +/- 11.8 ng/ml (37.75 +/- 14.5 to 58.25 +/- 29.5 nmol/l) (p < 0.001). Treatment led to > or = 5 ng/ml (12.5 nmol/l) increases in 25-hydroxyvitamin D level in 54% of treated patients, and only 25% achieved levels > or = 30 ng/ml (75 nmol/l). Mean iPTH level decreased from 157.9 +/- 125.9 to 150.7 +/- 127.5 pg/ml (p = 0.5). Only 26% of patients had > or = 30% decrease in their iPTH level after treatment with ergocalciferol. CONCLUSIONS: Current K/DOQI guidelines are inadequate for correcting VDDI or secondary hyperparathyroidism in CKD patients. Future studies should examine the effects of higher or more frequent dosing of ergocalciferol on these clinical endpoints.

Simultaneous development of Kaposi's sarcoma and lymphoma in a renal transplant recipient.

Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma are frequent complications of renal transplantation that usually occur as separate entities. We describe a young woman who simultaneously developed Kaposi's sarcoma and lymphoma after kidney transplantation. Immunosuppression consisted of cyclosporine and prednisone with normal serum creatinine. Fifteen months after transplantation, she developed Kaposi's sarcoma skin lesions, generalized lymphadenopathy, and ascites. A lymph node biopsy showed both Kaposi's sarcoma and lymphoma in the same tissue specimen with Epstein-Barr viral genomes within the tumor cells. Graft function remained normal. Cyclosporine was discontinued, and treatment with acyclovir was started, but the patient's condition rapidly deteriorated, and she died. This is the first case in which both Kaposi's sarcoma and lymphoma were present in the same biopsy specimen. After renal transplantation, more than one tumor can develop either simultaneously or in succession.

Serologic association of human herpesvirus eight with posttransplant Kaposi's sarcoma in Saudi Arabia.

BACKGROUND: This study investigates the association between human herpesvirus eight (HHV8) and Kaposi's sarcoma (KS), the most common cancer occurring in renal transplant recipients in Saudi Arabia. METHODS: A cross-sectional study of seroreactivity to HHV8 antigens in posttransplant KS patients from a tertiary care hospital in Riyadh, Saudi Arabia, and in control subjects without KS was conducted. Seroreactivity rates were determined using immunoblotting assays to detect antibodies to two lytic cycle HHV8 antigens: p40, an antigen found in infected cells, and sVCA, an HHV8-encoded small viral capsid antigen expressed in Escherichia coli. RESULTS: Antibodies to HHV8 p40 and sVCA were present in a significantly higher proportion of renal transplant patients with KS (13 of 14 patients) compared to renal transplant patients without KS (5 of 18; P<0.001) and compared to other control individuals (6 of 44; P<0.001). HHV8 seroreactivity was more common among patients with renal failure (28%) than among other control groups (7%). CONCLUSIONS: The serologic results provide evidence of a strong association between HHV8 and posttransplant KS in Saudi Arabia.

PIP: In Saudi Arabia, Kaposi's sarcoma occurs in 4.1% of renal transplant recipients and accounts for 70% of malignancies in this group. Human herpes virus 8 (HHV8) has been identified in the DNA of many of these patients. The association between HHV8 and Kaposi's sarcoma was investigated further in post-renal transplant Kaposi's sarcoma patients from a tertiary care hospital (King Faisal Specialist Hospital and Research Center) in Riyadh, Saudi Arabia (n = 14), and non-Kaposi's sarcoma controls with renal transplant (n = 18), chronic renal failure (n = 14), other cancers that did not affect renal function (n = 15), and healthy volunteers (n = 15). The median time from transplant to Kaposi's sarcoma was 13 months. A serum sample was assumed to have antibodies to HHV8 if antibody to either p40 or sVCA was detected. The prevalence of HHV8 seroreactivity was 13/14 (93%) in cases, 5/18 (28%) in renal transplants without Kaposi's sarcoma, and 11/62 (18%) in the aggregate control group. HHV8 seroreactivity was significantly more common (p 0.001) among transplant patients with Kaposi's sarcoma than those without this cancer (odds ratio, 33.80; 95% confidence interval, 2.96-904). These findings suggest an etiologic link between HHV8 and Kaposi's sarcoma presumably due to immunologic or cellular factors that influence host-virus interactions.

Improving utilization of intravenous immune globulin through concurrent use of an indication form.

OBJECTIVE: Based on the guidelines of the United States Joint Commission for Accreditation of Health Care Organizations for conducting a drug utilization evaluation, we evaluated the usage of intravenous immune globulin at our tertiary care hospital. METHODS: An initial concurrent evaluation of IVIG use showed deficiencies in both dosing and compliance with hospital policy, with regards to its use for unlabeled indications. Two follow-up evaluations were performed after the institution of an IVIG indication form, which was designed to accompany each order. RESULTS: We demonstrated consistent improvements in both dosing criteria, labeled IVIG use, and compliance with hospital policy its use in unlabeled indications. An ongoing prospective program targeting IVIG use, combined with the introduction of a simple indication form improved its utilization at our hospital.

Renal transplantation exposes patients with previous Kaposi's sarcoma to a high risk of recurrence.

It is currently estimated that about 0.5% of patients will develop Kaposi's sarcoma (KS) after kidney transplantation. Tapering of immunosuppression often leads to KS remission, but also results in graft loss in more than 50% of cases. Whether retransplantation is safe in these patients is unknown. We here report on eight patients who developed KS recurrence after kidney transplantation-(A) Patients with previously treated KS: There were 4 patients who had clinical remission of KS (including three posttransplantation) for periods ranging from 5 months up to 19 years before transplantation. All 4 developed KS recurrence within months after transplantation. In 3 patients, KS regressed only when all immunosuppression was discontinued, at the price of allograft removal. Partial remission occurred in the fourth patient following reduction of immunosuppression and gancyclovir administration; (B) Patients with recurrent KS during a single transplant: 4 patients developed KS after transplantation that regressed following reduction of immunosuppressive therapy. Increased immunosuppression, in the form of steroid pulses in 3 patients was associated with recurrence of KS. Subsequent reduction of immunosuppression caused regression of KS in all 4 patients, but 2 recipients lost their allografts. These data emphasize the high risk of recurrence of KS after renal transplantation. If physicians decide to transplant patients with a history of KS, they should inform the future recipient of the possibility of KS recurrence.

Hepatitis C virus infection in hemodialysis patients: comparison of two new hepatitis C antibody assays with a second-generation assay.

The performance of two new hepatitis C virus antibody (anti-HCV) assays (a third-generation immunoglobulin (Ig)G recombinant immunoblot assay (RIBA 3.0) and hepatitis C virus core IgM (HCV IgM) in the prediction of hepatitis C viremia in hemodialysis patients was compared with that of a second-generation IgG recombinant immunoblot assay (RIBA 2.0). Forty-three patients on maintenance hemodialysis were studied. Aliquots of sera were tested prospectively for anti-HCV by RIBA 2.0, RIBA 3.0, and HCV IgM and for HCV RNA by polymerase chain reaction. Thirty-eight patients were HCV RNA positive. Among those, 7 (18%) were HCV IgM positive, 22 (58%) were RIBA 2.0 positive, and 29 (76%) were RIBA 3.0 positive. All but one viremic patients detected by HCV IgM were also detected by RIBA 2.0 and RIBA 3.0. All viremic patients detected by RIBA 2.0 were also detected by RIBA 3.0. RIBA 3.0 was more sensitive than RIBA 2.0 and HCV IgM in the detection of viremic patients (P = 0.0156 and < 0.0001, respectively). The positive predictive value for HCV IgM was 100% as compared with 96 and 97% for RIBA 2.0 and RIBA 3.0, respectively. The negative predictive value for RIBA 3.0 was 36% as compared with 24 and 14% for RIBA 2.0 and HCV IgM, respectively. At 6-months follow-up of the eight viremic patients without a detectable IgM or IgG anti-HCV response, all patients remained RIBA 2.0 nonreactive, one became RIBA 3.0 indeterminate, and one became HCV IgM positive. These data suggest that HCV IgM has poor sensitivity in the detection of hepatitis C viremia and RIBA 3.0 improves the sensitivity of IgG anti-HCV assays in the early detection of hepatitis C viremia in hemodialysis patients.

Attitudes of commercial renal transplant recipients toward renal transplantation in India.

Renal transplantation offers patients with end-stage renal disease the best opportunity for rehabilitation and long-term survival. However, there is a critical shortage of transplantable kidneys worldwide. This plays well into the hands of transplanters and entrepreneurs involved in commercial renal transplantation, particularly in India. This practice has been condemned by all transplant societies. In our fight against rampant commercialism in renal transplantation, we sought to describe feelings of patients who had received transplants in India, and the difficulties they faced during their stay there. The results show that the two reasons that motivated patients to go to India were lack of living-related donors and the need for prompt transplant. More than half of the patients did not meet their donors. Their experience, however, has been largely positive except for some negative feelings toward the broker and the standard of hospital hygiene. The total cost of the transplant was far less than that in the West but, despite that, some patients felt financially exploited. Communication with them was poor, as most patients did not get adequate pretransplant education and were not informed of possible complications including rejection and graft loss. Furthermore, almost half of the patients were not given medical reports. These results substantiate the impression that CRT in India does not conform to the high standards of renal transplant medicine.

Impact of hepatitis C virus infection on kidney transplant outcome.

One hundred and forty kidney transplant recipients were evaluated to study the impact of hepatitis C virus (HCV) infection on patient and graft outcome. There .were 98 males arid 42 females with a mean age of 32.1 +/- 13 years. The duration of follow-up ranged from 6-60 months with a mean period of 27.8 +/- 18.2 months. Seventy-four (53%) patients had received cadaveric kidneys while 66 (47%) received living donor grafts. Anti-HCV reactivity was tested using second generation enzyme-linked immunosorbent assay and positivity was confirmed by recombinant immunoblot assay. HCV infection was diagnosed in 29 cases (20.7%) while HBsAg was found in nine (6.4%) and concomitant anti-HCV and HBsAg positivity was observed in two patients (1.4%). Seventeen of 29 (58.6%) patients with anti-HCV reactivity showed elevated ALT levels as against 17 of 111 (17.3%) anti-HCV non-reactive patients (P< 0.001). There was no association between the sex of the patient, source of the graft, and anti-HCV reactivity. Serum creatinine values were higher in the anti-HCV positive group, but this did not rank to statistical significance. We observed a significantly higher graft loss among the anti-HCV reactive group (27.6% versus 1.8%, P< 0.003). Thirteen anti-HCV reactive patients were subjected to 18 liver biopsies; the commonest lesion observed was chronic active hepatitis, which was progressive in two patients subjected to re-biopsy. We conclude that HCV infection is a serious health problem among kidney transplant recipients and it significantly affects the graft outcome.

Late recurrence of Wegener's granulomatosis presenting as tracheal stenosis in a renal transplant patient.

An unusual case of a 46-year-old man who had end-stage renal disease due to crescentic glomerulonephritis that was treated by a cadaveric renal allograft is presented. About 18 months post-Tx, the patient developed severe tracheal stenosis which, on biopsy, revealed granulation tissue and chronic inflammation. After another 18 months he developed necrotizing glomerulonephritis involving the renal allograft and an inflammatory retro-orbital pseudotumor. The latter, on biopsy, revealed granulomatous vasculitis characteristic of Wegener's granulomatosis. This diagnosis was further confirmed by strongly positive anti-neutrophil antibodies with diffuse granular cytoplasmic immunofluorescence (C-ANCA). The patient was treated successfully with cyclophosphamide therapy.

Kidney transplantations at King Faisal Specialist Hospital and Research Centre.

During the five year period from 1987G to 1991G, 161 kidney transplantations were performed at King Faisal Specialist Hospital and Research Centre (KFSH&RC); 79 from cadaveric donors (CD) and 82 from living related donors (LRD). All cadaveric kidneys except one were harvested within Saudi Arabia and 67% were from Saudi nationals. The immunosuppresive protocol was a triple drug regimen comprising cyclosporin-A (CyA), azathioprine (Aza), and prednisone. The actuarial graft survival rates at one and three years were 85% and 76% for the cadaveric donor transplants and 96% and 91%, respectively for the living related donor transplants (P<0.01). The corresponding patient survival rates for cadaveric donor transplants (CDTxs) were 97% and 94% and for the living related donor transplants (LRDTxs), 99% and 97% (NS). These results compare well with the best results in the Western world. The most serious surgical complications were vascular thromboses (five cases) and infections of the arterial anastomosis line with bleeding (two cases), all leading to loss of the cadaveric graft. The most common causes of death were virus infection, varicella, cytomegalovirus, and hepatitis B and C. The organ donation rate, from cadaveric donors as well as living related donors, is stil low in Saudi Arabia. Lack of organs is the main obstacle to an expansion of this promising transplantation activity. Continuous education of the multinational medical profession as well as the lay population is necessary to improve the situation.

The effect of extracorporeal high blood flow rate on left ventricular function during hemodialysis--an echocardiographic study.

The effect of increased extracorporeal blood flow rate on left ventricular (LV) function has been studied during volume-controlled bicarbonate hemodialysis. Ten stable patients on chronic hemodialysis, with a mean age of 28 years (range 19-38) were studied using two-dimensional and Doppler echocardiography. The mean time on hemodialysis was 32 months (range 3-60). All patients were investigated during three dialysis sessions on the first day of the week for 3 consecutive weeks. The blood flow rate was chosen randomly as 250, 350, or 450 cc/min. Apart from the time of hemodialysis and blood flow rate, other parameters of the hemodialysis were kept stable during all three sessions. Echocardiographic studies were done before, at mid dialysis, and during the last 15 min of each dialysis session. The following parameters were evaluated: heart rate, mean blood pressure, shortening fraction, ejection fraction, cardiac output, and pre-ejection period/LV ejection time ratio. The changes of the measured cardiac parameters at the beginning, middle and end of each session were not significantly different. Furthermore, the differences in changes between the three different sessions were comparable. Our results indicate that an increase in dialysis blood flow rate up to 450 cc/min does not have an adverse effect on the left ventricle in patients on maintenance hemodialysis and with stable cardiovascular function.