Pain affects health-related quality of life in kidney transplant recipients

BACKGROUND: Chronic pain is prevalent in end-stage renal disease patients undergoing chronic hemodialysis. We do not fully know the intensity of chronic pain experienced by kidney recipients in comparison to those on chronic hemodialysis and healthy controls. Moreover, the effect of chronic pain on kidney recipients' health-related quality of life (HRQoL) is yet to be comprehensively addressed. We designed this study to find an answer to these questions. METHODS: In this case control study, we studied 205 kidney recipients, 69 hemodialysis patients, and 100 healthy controls, who were matched for age, sex, monthly family income, and educational level. The patients were evaluated for the intensity of chronic pain by Visual Analogue Scale (VAS). HRQoL was measured with Short Form 36 (SF-36) in the kidney recipients. Chronic pain intensity was compared in the study groups, and in the kidney recipients the correlation between SF-36 subscores and severity of pain was assessed. RESULTS: Severity of pain in the kidney recipients was lower than the hemodialysis patients, but more than the healthy controls (P=.001). The VAS pain score negatively correlated with the scores of SF- 36 total (r=-.329, P=01), mental health (r=-.190, P=07), physical health (r=-.275, P=.001), physical function (r=-.339, P=.001), role limitation due to physical problems (r=-.478, P=.001), role limitation due to emotional problems (r=-.326, P=.001), and bodily pain (r=-.894, P=.001). DISCUSSION: The intensity of chronic pain experienced by the kidney recipients is less than that experienced by patients under chronic hemodialysis, but higher than healthy subjects. Focusing on chronic pain as a cause of post-renal transplantation morbidity is expected to improve post-renal transplantation quality of life.     

Pregnancy in kidney transplant recipients

PURPOSE: Our aim was to investigate kidney allograft, obstetric, and maternal outcomes in pregnant women undergoing kidney transplantation in our center. METHODS: Retrospective data on 74 pregnancies in 60 patients were reviewed and completed through phone interviews were compared with information on a control group of female kidney recipients. RESULTS: Mean age of patients at transplantation was 26.55 +/- 4.72 years and the median interval between transplantation and pregnancy was 27.5 months. Gestational period was 8 months. Live birth was the outcome in 43.2% of pregnancies; 9.5% led to still birth, 24.3% were aborted, and obstetrical data of the remaining were unavailable. Among the 11 patients who became pregnant within 12 months after transplantation, we observed seven live births and four abortions. None of pregnancies that were accompanied by acute rejection episodes (ARE) were successful. Twenty-six patients experienced at least one ARE versus 23 patients of the control group (P = NS). However, the first ARE occurred later in the pregnant group (P = .028). Chronic rejection and graft loss were seen in 24 and 18 study group cases and 17 and 17 control cases, respectively (P = NS). One-, 3-, 5-, and 10-year graft survivals were 100%, 96.5%, 94.5%, and 77.1% in the pregnant group versus 93.2%, 85.7%, 81%, and 64.7% in the control group, respectively (P = .07). CONCLUSION: Pregnancy in kidney recipients seems to be safe for kidney allograft recipients even within the first year posttransplant. Nonetheless, the outcomes of pregnancy in this group of patients is not always favorable, especially when rejection occurs simultaneously.     

Cryoglobulinemia in kidney transplant recipients

The aim of this study was to assess the presence of cryoglobulins, the constitution of the cryoprecipitate, as well as the possible etiology and clinical features in kidney transplant recipients. We excluded patients with clinical or laboratory evidence of autoimmune, liver or neoplasm disease, infections, blood transfusions or immunizations in the previous 3 months. Detection of cryoglobulins was obtained from the peripheral venous blood. In cases of cryoprecipitate formation it was analyzed using anti-IgG, anti-IgM, anti-IgA, anti-C3, and anti-C4 antibodies. The hepatitis C virus (HCV) was detected by the polymerase chain reaction. Thirty-nine patients were selected, of whom 23 were men and the overall mean age was 40.6 +/- 12.7 years. Cryoprecipitate was detected in 74.4% (29/39) patients. Among patients with or without cryoprecipitate formation, the serum creatinine values, the percentage of patients with proteinuria, and the posttransplantation times were similar. In patients with cryoglobulins, 37.9% (11/29) were HCV positive. The etiology was not determined for the other patients. The IgG, IgM, and IgA immunoglobulins and the complement fractions C3 and C4 were found in the cryoprecipitate. Their compositions were similar among patients with or without HCV. Few clinical features were associated with the presence of cryoglobulins, including deep venous thrombosis, cutaneous purpura and peripheral neuropathy. In conclusion, cryoglobulinemia was prevalent in kidney transplant recipients, but appeared to not affect graft function. HCV infection was the most frequently associated etiology and clinical features were infrequent.     

Hypertension in kidney transplant recipients

Arterial hypertension is frequently observed in renal transplant recipients. Its pathogenesis is multifactorial in most cases. Calcineurin inhibitors (CNI) can increase peripheral vascular resistance by inducing arteriolar vasoconstriction and can cause extracellular fluid expansion by reducing the glomerular filtration rate (GFR), activating the renin–angiotensin system (RAS), and by inactivating the atrial natriuretic peptide. Glucocorticoids can impair urinary water and salt excretion. Poor graft function can lead to increased extracellular volume and inappropriate production of renin. Native kidneys, older age of the donor and transplant renal artery stenosis (TRAS) may also contribute to the development of hypertension. Arterial hypertension not only can increases the risk for cardiovascular events but can also deteriorate renal allograft function. A number of studies have shown that the higher the levels of blood pressure are, the higher is the risk of graft failure. On the other hand, a good control of blood pressure may prevent many cardiovascular and renal complications. Appropriate lifestyle modification is the first step for treating hypertension. Calcium channel blockers (CCB) and renin–angiotensin system (RAS) inhibitors are the most frequently used antihypertensive agents, but in many cases, a combination of these and other drugs is required to obtain good control of hypertension.     

Fatigue in kidney transplant recipients

Fatigue is still present in approximately 40%‐50% of kidney transplant recipients (KTR), rates comparable to that of the hemodialysis population. Correlates of fatigue include inflammation, symptoms of depression, sleep disorders, and obesity. Fatigue in KTR determines a significant severe functional impairment, either when globally considered or when analyzed at the level of the single domains such as sleep and rest, homemaking, mobility, social interaction, ambulation, leisure activities, alertness behavior, and work limitations. In addition, fatigue in KTR is significantly associated with a severe deterioration of quality of life. Fatigue is very common among KTR poorly adherent to immunosuppressive therapy. Unfortunately, there is no evidence of studies about the treatments of this symptom in KTR. Efforts to detect and treat fatigue should be a priority in order to improve quality of life of KTR.     

A clinical tool to risk stratify potential kidney transplant recipients and predict severe adverse events

Preoperative risk assessment of potential kidney transplant recipients often fails to adequately balance risk related to underlying comorbidities with the beneficial impact of kidney transplantation. We sought to develop a simple scoring system based on factors known at the time of patient assessment for placement on the waitlist to predict likelihood of severe adverse events 1 year post‐transplant. The tool includes four components: age, cardiopulmonary factors, functional status, and metabolic factors. Pre‐transplant factors strongly associated with severe adverse events include diabetic (OR: 3.76, P<.001), coronary artery disease (OR: 3.45, P<.001), history of CABG/PCI (OR 3.1, P=.001), and peripheral vascular disease (OR 2.74, P=.008).The score was evaluated by calculation of concordance index. The C statistic of 0.74 for the risk stratification group was considered good discrimination in the validation cohort (N=127) compared to the development cohort (N=368). The pre‐transplant risk group was highly predictive of severe adverse events (OR 2.36, P<.001). Patients stratified into the above average‐risk group were four times more likely to experience severe adverse events compared to average‐risk patients, while patients in the high‐risk group were nearly 11 times more likely to experience severe adverse events. The pre‐transplant risk stratification tool is a simple scoring scheme using easily obtained preoperative characteristics that can meaningfully stratify patients in terms of post‐transplant risk and may ultimately guide patient selection and inform the counseling of potential kidney transplant recipients.     

Increased intracellular adenosine triphosphate level as an index to predict acute rejection in kidney transplant recipients

Background: Peripheral blood CD4 + T cell adenosine triphosphate (ATP) release has been reported to be an adjunct tool to evaluate global cellular immune response in solid-organ transplant recipients. However, the correlation between the ATP level and rejection was controversial. The aim of this prospective clinical study was to explore the association between the intracellular ATP level and the occurrence, progression, and treatment of acute rejection (AR) episodes, determine the predicting value of intracellular ATP level for AR in kidney transplant (KT) recipients. Patients and methods: In the period of October 2011 to October 2012, 140 KT recipients were recruited and followed for six months after transplantation. Patients were categorized into stable group and AR group according to their clinical course. Whole blood samples were collected pretransplantation, and at 7, 14, 21, and 28 days, and at 2, 3, 4, 5 and 6 months post-transplantation. Additional blood samples were obtained from AR patients on the day AR occurred, on the day before and 3 and 7 days after intravenous anti-rejection therapy started, and on the day when AR reversed. The intracellular ATP in CD4 + T cells was detected by ImmuKnow Immune Cell Function Assay according to the manufacturer's instruction. The absolute number of CD4 + T cells and the trough levels of tacrolimus and cyclosporine were also measured. Results: The ATP level detected on the day AR occurred (627.07 ± 149.85 ng/ml) was obviously higher than that of the stable group (320.48 ± 149.11 ng/ml, P < 0.05). ATP value decreased to 265.35 ± 84.33 ng/m at the end of anti-rejection therapy, which was obviously lower than that measured on the day before the anti-rejection therapy started (665.87 ± 162.85 ng/ml, P < 0.05). ROC analysis revealed that increased intracellular adenosine triphosphate level showed better sensitivity and specificity than those obtained using single time point detection (89.5% vs 85.0%;95.0% vs 88.9%). The best cutoff value was 172.55 ng/ml. A positive correlation between the intracellular ATP level and absolute CD4 + T cell number (r = 0.656, P < 0.001) was found in the patients with CD4 + T cell counts < 200/μl.     

Aortic reconstruction in kidney transplant recipients

Renal transplantation has increased the longevity of patients with uremia. An increasing number undergo aortic reconstruction, which exposes the transplanted kidney to ischemic injury. To evaluate the risk for renal failure, loss of the transplant, and methods of renal protection, we reviewed our experience. Clinical data were reviewed for 10 consecutive patients (7 men, 3 women; mean age 52.7 years [range 32 to 75 years]) with a transplanted kidney who underwent aortic reconstruction between 1977 and 1994 at our institution. Mean interval between renal transplantation and aortic reconstruction was 5.9 years (range 1 month to 12.7 years). Seven patients required emergency repair because of dissection (2 patients), aneurysm rupture (4 patients), or symptomatic aneurysm (1 patient); three underwent elective repair. Reasons for reconstruction included aortic dissection (2 patients), aneurysm of the descending thoracic (2 patients), thoracoabdominal (1 patient), or abdominal aorta (3 patients), and aortoiliac occlusive disease (2 patients). Patients with thoracic or thoracoabdominal reconstructions underwent repair with atriofemoral, aortofemoral, or femorofemoral shunt placement or bypass. Of the five abdominal aortic reconstructions, the kidney was protected with aortofemoral shunt placement in one patient and cold renal perfusion in three. In two of them, topical cooling of the kidney also was used. One patient with acute aortic dissection died at 39 days as a result of respiratory failure. Loss of the recently transplanted kidney was caused by acute rejection. One patient had a transient increase in serum creatinine concentration. Eight had no worsening of renal function, and none of the nine survivors lost the transplanted kidney. We conclude that aortic reconstruction can be safely performed in kidney transplant recipients. Patients in whom thoracic or thoracoabdominal aortic reconstruction was required were protected with an atriofemoral or aortofemoral bypass or shunt. Patients undergoing abdominal aortic reconstruction did well when cold renal perfusion with or without local cooling of the transplant was used for renal protection. Transplanted kidneys appeared to tolerate ischemic injury similarly to native kidneys.Presented at the Twentieth Annual Meeting of the Peripheral Vascular Surgery Society, New Orleans, La., June 10, 1995.     

Urinary metabolites predict prolonged duration of delayed graft function in DCD kidney transplant recipients

Extending kidney donor criteria, including donation after circulatory death (DCD), has resulted in increased rates of delayed graft function (DGF) and primary nonfunction. Here, we used Nuclear Magnetic Resonance (NMR) spectroscopy to analyze the urinary metabolome of DCD transplant recipients at multiple time points (days 10, 42, 180, and 360 after transplantation). The aim was to identify markers that predict prolonged duration of functional DGF (fDGF). Forty‐seven metabolites were quantified and their levels were evaluated in relation to fDGF. Samples obtained at day 10 had a different profile than samples obtained at the other time points. Furthermore, at day 10 there was a statistically significant increase in eight metabolites and a decrease in six metabolites in the group with fDGF (N = 53) vis‐à‐vis the group without fDGF (N = 22). In those with prolonged fDGF (≥21 days) (N = 17) urine lactate was significantly higher and pyroglutamate lower than in those with limited fDGF (<21 days) (N = 36). In order to further distinguish prolonged fDGF from limited fDGF, the ratios of all metabolites were analyzed. In a logistic regression analysis, the sum of branched‐chain amino acids (BCAAs) over pyroglutamate and lactate over fumarate, predicted prolonged fDGF with an AUC of 0.85. In conclusion, kidney transplant recipients with fDGF can be identified based on their altered urinary metabolome. Furthermore, two ratios of urinary metabolites, lactate/fumarate and BCAAs/pyroglutamate, adequately predict prolonged duration of fDGF.     

Treating gout in kidney transplant recipients

OBJECTIVE: To review the etiology, treatment, and preventive strategies of hyperuricemia and gout in kidney transplant recipients. DATA SOURCES: Primary literature was obtained via Medline (1966-June 2003). STUDY SELECTION AND DATA EXTRACTION: Studies evaluating treatment and prevention of hyperuricemia and gout in kidney transplantation were considered for evaluation. English-language studies were selected for inclusion. DATA SYNTHESIS: Approximately 14,000 kidney transplantations were performed in the United States in 2003, and of those transplant recipients, nearly 13% will experience a new onset of gout. The prevalence of hyperuricemia is even greater. There are several mechanisms by which hyperuricemia and gout develop in kidney transplant recipients. Medication-induced hyperuricemia and renal dysfunction are 2 of the more common mechanisms. Prophylactic and treatment options include allopurinol, colchicine, corticosteroids, and, if absolutely necessary, nonsteroidal antiinflammatory drugs. CONCLUSION: It is generally recommended to decide whether the risks of prophylactic therapy and treatment outweigh the benefits. Often, the risk of adverse events associated with agents to treat these ailments tends to outweigh the benefits; therefore, treatment is usually reserved for symptomatic episodes of acute gout. Practitioners must also decide if changes in immunosuppressive regimens may be of benefit on a patient-by-patient basis.     

Vascular access in kidney transplant recipients

Vascular access is an important element in the overall care provided to kidney transplant recipients. The transplanted kidney is not indestructible, and chronic kidney disease after transplantation may result in needing another transplant or beginning dialysis. Commonly used vascular accesses, like peripheral and central lines, can preclude the creation of future, permanent dialysis access. Therefore, there is urgent need to preserve vessels for the future access needs for hemodialysis among kidney transplant recipients without functional vascular access for dialysis. Moreover, the proper care of functional vascular access among kidney transplant recipients is crucial. In this review article, we will address the common vascular access procedures and complications among kidney transplant recipients.     

Posttransplant diabetes in kidney transplant recipients

We retrospectively reviewed the course of 1,000 renal transplants performed in 835 recipients (758 nondiabetics) to assess the incidence of new onset posttransplant diabetes in former nondiabetics. A total of 119 (15.7%) recipients manifested posttransplant diabetes, of whom 64 (53.8%) became hyperglycemic within 3 weeks of transplantation. Actuarial survival analysis indicated a statistically significant selection of blacks; 68 (57.1%) in the group of posttransplant diabetics contrasted with 30.4% of the overall series who were black (p = less than 0.01). Males comprised 73 (61.3%) of posttransplant diabetics, consistent with the male proportion of 66.6% in the entire series. The total dose of methylprednisolone administered before onset of posttransplant diabetes was less than 2.5 g in 86 (69%) and less than 5 g in 110 (92%) patients. Familial diabetes had been noted in 12 (10%) posttransplant diabetics and in 10 (9%) controls. New cases of posttransplant diabetes occurred at a relatively constant annual rate over the decade of study (+/- 15%/year). Patient survival in controls was greater than in posttransplant diabetics, reaching significance (83 vs. 67%) at 2 years. Kidney graft survival in controls and posttransplant diabetics was similar. We conclude that posttransplant diabetes is of greater prevalence in blacks, is not proportional to total dose or duration of intravenous methylprednisolone therapy, and imposes a threat to recipient survival.     

Neurological complications in kidney transplant recipients

Neurological complications are frequent in renal transplant recipients and may largely contribute to morbidity and mortality. The postransplant neurological complications may be categorized into five areas: 1) Immunosuppressive medications, 2) stroke, 3) peripheral neuropathies, 4) infection, and 5) malignancies. A number of complications are directly caused by the neurotoxicity of immunosuppressive agents. Calcineurin-inhibitors may cause mild symptoms, such as tremors and paresthesia, or severe symptoms, such as disabling pain syndrome and leukoencephalopathy. Severe neurological syndromes may also be caused by the monoclonal antibody OKT3. Stroke may occur in about 8% of renal transplant patients. It may be favored by hypertension, diabetes, and accelerated atherosclerosis which may be acquired during dialysis or after transplantation. Peripheral mononeuritis and polyneuritis may also occur. An acute femoral neuropathy may occur in about 2% of patients as a result of nerve compression after operation. Guillain-Barré syndrome may also develop, triggered in some cases by cytomegalovirus (CMV) or Campylobacter jejuni infection. Lymphomas are the most frequent brain tumors. They are usually associated to a Epstein Barr virus (EBV) infection and are more frequent in patients who received an aggressive immunosuppressive therapy. Infection represents the most frequent neurological complication. Acute meningitis usually caused by Listeria monocytogenes, subacute and chronic meningitis caused by Cryptococcus neoformans, focal brain infection caused by Aspergillus fumigatus, Toxoplasma gondii or Nocardia asteroids, and progressive dementia caused by polyoma J virus or other viruses are the most frequent types of neurological infections.     

Liver disease in kidney transplant recipients

Kidney transplant recipients can develop acute and chronic liver disease from a variety of conditions. Chronic viral hepatitis from hepatitis C is seen in increased frequency in hemodialysis patients. Genetic conditions, such as polycystic kidney disease, which lead to the need for kidney transplantation are also associated with liver diseases including congenital hepatic fibrosis and polycystic liver disease.Other conditions that can induce liver disease in this immune-suppressed population include a multitude of viral infections, as well as other systemic infections that can involve the liver. Drug induced liver injury is also seen in increased rates due to the use of poly-pharmacy, the effect of immune-suppression on drug metabolizing pathways in the liver and the potential of drug to drug interactions.Post transplant metabolic syndrome is also increased in kidney transplant recipients and this can lead to development of non-alcoholic fatty liver disease.A knowledge of the presentation of these liver diseases is essential in diagnosing the cause of liver disease as well as informing the diagnostic workup. Specific therapies for the various conditions will also be discussed in this review.