Routine ultrasonography surveillance of native kidneys for renal cell carcinoma in kidney transplant candidates.

Renal cell carcinoma (RCC) has a high incidence in the kidney transplant population and annual surveillance detects these tumors early in their natural history. Minimal guidelines exist regarding RCC surveillance in ESRD patients awaiting transplant. A retrospective review of our kidney transplant database examined the outcomes of annual ultrasonographic surveillance during initial kidney transplant evaluation and upon annual reassessment. Of 2642 patients listed for transplant, 145 patients were found to have masses during initial kidney transplant evaluation or annual imaging consistent with new complex cystic disease or RCC. A total of 71 patients had RCC identified, with 52 found on initial kidney transplant evaluation and 19 identified on annual surveillance. Male gender and African-American race were independently associated with RCC (P<.05). RCC was detected a median of 2.0 years after listing (two annual ultrasonography studies). Patients with complex cysts were more likely to undergo transplantation (48.7%) compared to patients with RCC (21.1%; P<.001). There was no significant difference in survival between RCC patients and those found to have complex cystic disease, suggesting incidental RCC can be diagnosed early in the natural history and at a curable stage through implementation of a biennial surveillance program.

Acute kidney injury following liver transplantation: definition and outcome.

The incidence of acute kidney injury (AKI) has been reported to vary between 17% and 95% post-orthotopic liver transplantation. This variability may be related to the absence of a uniform definition of AKI in this setting. The purpose of this study was to identify the degree of AKI that is associated with long-term adverse outcome. Furthermore, to determine the best definition (for use in future studies) of AKI not requiring dialysis in post-liver transplant patients, we retrospectively reviewed the effect of 3 definitions of AKI post-orthotopic liver transplantation on renal and patient outcome between 1997 and 2005. We compared patients with AKI to a control group without AKI by each definition. AKI was defined in 3 groups as an acute rise in serum creatinine, from the pretransplant baseline, of >0.5 mg/dL, >1.0 mg/dL, or >50% above baseline to a value above 2 mg/dL. In all groups, the glomerular filtration rate was significantly lower at both 1 and 2 years post-transplant. Patient survival was worse in all groups. Graft survival was worse in all groups. The incidence of AKI was highest in the group with a rise in creatinine of >0.5 mg/dL (78%) and lowest in patients with a rise in creatinine of >50% above 2.0 mg/dL (14%). Even mild AKI, defined as a rise in serum creatinine of >0.5 mg/dL, was associated with reduced patient and graft survival. However, in comparison with the other definitions, the definition of AKI with the greatest impact on patient's outcome post-liver transplant was a rise in serum creatinine of >50% above baseline to >2 mg/dL.

West Nile virus encephalitis in a renal transplant recipient: the role of intravenous immunoglobulin.

West Nile virus is a common viral infection in endemic areas. Although the disease has a benign course in immunocompetent individuals, it tends to run a more malignant course in immunocompromised patients such as solid-organ transplant recipients. In this study, a renal transplant recipient presented with fever, impaired speech, obtundation, and features suggestive of meningitis on cerebrospinal fluid examination. Although initial serological study results were negative, the patient was treated promptly with intravenous immunoglobulin (IVIG) based on a strong clinical suspicion of West Nile virus encephalitis. Therapy with IVIG was associated with complete recovery of neurological features, and the patient was discharged on day 7 after resolution of neurological complications. The favorable outcome of this patient may be related to early treatment with IVIG.

Hypertension and kidney disease: a deadly connection.

Kidney disease may be the cause or a consequence of hypertension. Hypertension affects 25% of the adult population in the United States. Similarly, chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been steadily increasing in incidence because of the increasing age of the US population and rise in the incidence of risk factors, including hypertension. Substantial evidence supports the notion that elevated blood pressure is the most significant risk factor for developing CKD. Microalbuminuria has been shown to be the early marker of hypertensive renal disease. Furthermore, therapy to reduce microalbuminuria was associated with delayed progression of renal disease. Black Americans are at higher risk for developing hypertensive nephrosclerosis than whites. Hypertension is a major risk factor for cardiovascular events in patients with CKD and ESRD and those who have undergone renal transplantation. Studies have documented that elevated serum creatinine and CKD are risk factors for a cardiovascular event. Tight blood pressure control has been shown to reduce microalbuminuria and proteinuria and to delay progression of renal disease. Tailoring antihypertensive medication to the clinical setting to achieve a blood pressure goal is critical in reducing complications from this deadly connection.

Liver and kidney transplantation for polycystic liver and kidney-renal function and outcome.

BACKGROUND: Polycystic liver disease (PLD) is a rare disorder frequently associated with polycystic kidney disease (PKD). Transplantation is a treatment option for these patients. Because of preservation of hepatic function in these patients, liver transplantation is not routinely utilized. We report a large series of PLD patients and their outcomes following liver and kidney transplantation. METHODS: Fourteen patients underwent orthotopic liver transplantation (OLTx) for PLD between 1987 and 2003. Twelve patients had PKD combined with PLD. Nine patients received only liver transplantation. Five patients had combined liver and kidney transplantation. Thirteen patients (93%) survived for at least one year following liver transplantation. Two out of eight patients who received solitary liver transplantation later required kidney transplantation. RESULTS: Pretransplant glomerular filtration rate (GFR) in patients with PKD was 75.8+/-25.4 ml/min/1.73 m. One year later, GFR was 37.2+/-8.3 ml/min/1.73 m. Kaplan-Meier analysis showed that one- and two-year graft survival for combined liver and kidney transplantation was 80% (n=5), whereas graft survival for solitary liver transplantation was 100% (n=9). Mean survival of patients who had combined liver and kidney transplantation was 46.7+/-54.2 months (n=5), whereas the mean survival for solitary liver transplant patients was 80.4+/-68.6 months (n=9) (P=0.36). CONCLUSION: Transplantation is an excellent option for PLD with dramatic improvement in quality of life and acceptable morbidity. For combined liver and kidney transplantation one- and two-year patient survival rates were similar to combined transplantation for other indications. For patients with acceptable renal function at time of transplantation, solitary liver transplantation has an excellent outcome.

Systolic blood pressure is the main etiology for poorly controlled hypertension.

BACKGROUND: Isolated systolic hypertension is an important risk factor for cardiovascular events. The purpose of this study was to detect the prevalence of and to evaluate the effectiveness of currently available medications in the treatment of uncontrolled isolated systolic hypertension. METHODS: We randomly selected a total of 585 patients with hypertension from our database. The two most recent blood pressure (BP) readings and other data were obtained by chart review. RESULTS: Of 585 patients, 340 (58%) had controlled BP. Of 245 patients with uncontrolled hypertension, 77.1% had uncontrolled isolated systolic hypertension and the remaining 22.9% had uncontrolled diastolic hypertension. Patients with uncontrolled systolic hypertension were on average taking more antihypertensive medications than patients with controlled BP (2.10 +/- 0.09; P = .034). CONCLUSIONS: Systolic hypertension is the etiology of uncontrolled hypertension in the majority of patients. Currently available antihypertensive medications are less effective in controlling systolic hypertension.

Definition of chronic kidney disease after uninephrectomy in living donors: what are the implications?

BACKGROUND: Living kidney transplant donors generally have a favorable renal functional outcome postuninephrectomy, but concern remains that a reduced glomerular filtration rate (GFR) postuninephrectomy might have harmful effects. This study examines the short-term (3 months) effect of donor nephrectomy on GFR and the occurrence of stage 3 chronic kidney disease (CKD) postuninephrectomy. METHODS: The prevalence of stage 3 CKD (Kidney Disease Quality Outcome Initiative [GFR<60 mL/min/1.73 m]) was examined in 196 living donors by comparing preuninephrectomy and 3-month postuninephrectomy values of GFR using I-iothalamate GFR (iGFR), modification of diet in renal disease estimated GFR (eGFR), Cockcroft-Gault estimated creatinine clearance, and endogenous 24-hr creatinine clearance. The accuracy of GFR estimations for predicting iGFR was also studied. RESULTS: The mean GFR before and after donation were iGFR, 105+/-18 and 68+/-13 mL/min/1.73 m; eGFR, 98+/-19 and 63+/-12 mL/min/1.73 m; Cockcroft-Gault estimated creatinine clearance, 125+/-33 and 85+/-22 mL/min/1.73 m, and endogenous 24-hr creatinine clearance, 133+/-38 and 86+/-24 mL/min/1.73 m, respectively. Stage 3 CKD was found postuninephrectomy in 53 donors (27%) by iGFR and in 73 donors (38%) by eGFR. The prevalence of stage 3 CKD was greater with older age. GFR estimation equations did not accurately predict iGFR, particularly postuninephrectomy. CONCLUSIONS: Stage 3 CKD is commonly observed after living kidney donation, particularly in older donors. The long-term impact of stage 3 CKD postuninephrectomy is poorly understood and may not have the same implications as stage 3 CKD in other conditions. eGFR is a poor predictor of true GFR in kidney donors.

Hepatorenal syndrome: a proposal for kidney after liver transplantation (KALT).

Hepatorenal syndrome (HRS) is a well-recognized complication of end-stage liver disease. Once thought to be a reversible condition with liver transplantation (LT) alone, HRS may directly contribute to the requirement for long-term dialysis posttransplant. As a result, discussion has now focused on whether or when a kidney allograft should be considered for these patients. Using the International Ascites Club guidelines with a pretransplant serum creatinine (SCr) >2.0 mg/dL to define HRS, 130 patients undergoing LT over a 10-yr period were identified, for an overall incidence of 9%. Patient survival rates at 1, 3, and 5 yr were 74%, and 68%, and 62%, respectively. Survival was significantly worse when compared to non-HRS patients undergoing LT over the same study period (P = 0.0001). For patients presenting with type 2 HRS, 7 patients (6%) developed irreversible kidney failure posttransplant compared to 0.34% in the non-HRS population (P < 0.0001). Five of these patients died within 1 yr with a median survival time of 139 days. Combined liver and kidney transplantation (CLKT) for patients with HRS is not recommended. However, an improvement in outcome can be accomplished by addressing those patients who require dialysis greater than 60 days posttransplant. We propose a role for kidney after liver transplantation (KALT) in select HRS patients.

Hypertension and kidney disease: a deadly connection.

Kidney disease may be the cause or a consequence of hypertension. Hypertension affects 25% of the adult population in the United States. Similarly, chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been steadily increasing in incidence because of the increasing age of the US population and rise in the incidence of risk factors, including hypertension. Substantial evidence supports the notion that elevated blood pressure is the most significant risk factor for the development of CKD. Microalbuminuria has been shown to be the early marker of hypertensive renal disease. Furthermore, therapy to reduce microalbuminuria was associated with delay in the progression of renal disease. Black Americans are at higher risk for developing hypertensive nephrosclerosis than whites. Hypertension is a major risk factor for cardiovascular events in patients with CKD and ESRD and those who have undergone renal transplantation. Studies have documented that elevated serum creatinine and CKD are risk factors for a cardiovascular event. Tight blood pressure control has been shown to reduce microalbuminuria and proteinuria and to delay progression of renal disease. Tailoring the choice of antihypertensive medication to the clinical setting to achieve a blood pressure goal is critical in reducing complications from this deadly connection.

Microalbuminuria, insulin resistance, diabetes, hypertension, and kidney function: the latest concepts in pathology and pharmacologic treatment.

Microalbuminuria-increased urinary albumin excretion undetectable by traditional urinary dipstick-has been associated with insulin resistance, diabetes mellitus, obesity, and hypertension. It is also a powerful predictor for heart disease and all-cause mortality. In diabetic patients, microalbuminuria has been correlated with the progression of diabetic nephropathy and the development of renal insufficiency. Furthermore, its correlation with markers of inflammation such as C-reactive protein suggests that microalbuminuria may indicate generalized endothelial dysfunction rather than isolated nephropathy. Drugs that block the renin-angiotensin system, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), have been shown to reduce albuminuria, resulting in renal protection. Recently, dualaction beta-adrenergic blockers such as carvedilol have been shown to exert favorable effects on albuminuria in diabetic patients with hypertension. Insulin resistance reflects a predictable risk for diabetes, and there appears to be a good correlation between insulin resistance, albuminuria, and progression of renal disease in diabetes with or without hypertension. As in microalbuminuria, ACE inhibitors, ARBs, and dual-action beta-blockers help improve insulin sensitivity.

Carbamylated low-density lipoprotein induces death of endothelial cells: a link to atherosclerosis in patients with kidney disease.

BACKGROUND: The presence of accelerated atherosclerosis in patients with kidney disease cannot be entirely explained by traditional cardiovascular risk factors. Exposure to urea, which is normally present in human blood plasma and elevated in patients with kidney disease, leads to the carbamylation of proteins. We postulated that low-density lipoprotein (LDL) carbamylated by urea has biologic effects relevant to atherosclerosis. METHODS: To produce carbamylated LDL (cLDL), human native LDL (nLDL) was chemically modified in vitro by exposure to potassium cyanate. Human coronary artery endothelial cells (HCAECs) and human coronary artery smooth muscle cells (CASMCs) were treated in vitro with cLDL or nLDL. Irreversible cell death was measured using the lactate dehydrogenase (LDH) assay, apoptosis was assessed by annexin V binding, and proliferation was determined using bromodeoxyuridine (BrdU) incorporation. Total plasma protein carbamylation and plasma cLDL were measured in hemodialysis patients using the homocitrulline assay and enzyme-linked immunosorbent assay (ELISA). RESULTS: Our studies demonstrated that cLDL but not nLDL induced dose-dependent vascular cell injuries relevant to atherosclerosis, which included the proliferation of vascular smooth muscle cells and endothelial cell death. Under light microscopy, endothelial cells treated with cLDL showed signs of morphologic alterations. The injury to endothelial cells measured by LDH release was time-dependent and correlated with the degree of LDL carbamylation. At least a part of the endothelial cell population treated with cLDL died by apoptosis. In patients with advanced renal disease on hemodialysis, total plasma protein carbamylation and plasma cLDL were several times higher than in control healthy individuals. CONCLUSION: Collectively these data suggest the potential role of carbamylated LDL in accelerated atherosclerosis in patients with chronic renal disease and, possibly, in healthy individuals.

Podocyte injury associated glomerulopathies induced by pamidronate.

BACKGROUND: Pamidronate has been demonstrated to decrease bone-related complications in multiple myeloma and delay progression of the disease. This has led to its use in supportive and maintenance therapy of myeloma in conjunction with steroids and chemotherapy. It has also been selectively used in patients with breast cancer and other neoplasms. METHODS: We report on five patients who developed glomerular disease induced by pamidronate. Pamidronate was the only drug common to all patients. Tests for hepatitis B and C and human immunodeficiency virus (HIV) were negative for all patients. The first two patients received a high dose of pamidronate for 8 weeks, whereas the other three patients were on monthly therapy for a prolonged period of time. Sources of data included chart review and pathologic analysis of kidney biopsy. RESULTS: Three patients were female and two were males and all were Caucasian, ranging in age from 58 to 71 years. Renal biopsy findings included minimal change disease in two, focal segmental glomerulosclerosis in two, and collapsing focal segmental glomerulosclerosis in one. Immunofluorescence was essentially negative in all cases. Electron microscopy showed variable podocyte injury and extensive foot process effacement. There was no evidence of multiple myeloma-related renal disease. After the biopsy, pamidronate was discontinued and renal function stabilized in all patients except the one with the collapsing variant of focal segmental glomerulosclerosis who required hemodialysis. Three patients had resolution of proteinuria, one patient continued to have proteinuria without deterioration in renal function. CONCLUSION: Pamidronate has been mainly associated with collapsing focal segmental glomerulosclerosis. This report expands that relationship and adds other glomerular diseases linked with podocyte injury. Additional studies are needed to define the cause of the variability of renal histology with this agent.

The Calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism.

Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in many patients with secondary hyperparathyroidism due to end-stage renal disease, but hypercalcemia, hyperphosphatemia, or both often develop during treatment. As such, alternative therapeutic approaches to managing excess PTH secretion are needed. Calcimimetic agents directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid glands, but clinical experience with them is limited. Fifty-two hemodialysis patients with secondary hyperparathyroidism were given single orally administered doses of the calcimimetic agent AMG 073 ranging from 5 to 100 mg, or placebo. Plasma PTH levels decreased 2 h after 25-, 50-, 75-, or 100-mg doses, falling by a maximum of 43 +/- 29%, 40 +/- 36%, 54 +/- 28%, or 55 +/- 39%, respectively. Plasma PTH levels decreased in all patients given doses of > or =25 mg but did not change in those who received placebo. In patients treated with daily doses of 25 or 50 mg of AMG 073 for 8 d, plasma PTH levels declined for the first 3 to 4 d and remained below baseline values after 8 d of treatment. Serum calcium concentrations also decreased by 5 to 10% from pretreatment levels in patients given 50 mg of AMG 073 for 8 d, but values were unchanged in those who received lower doses. Serum phosphorus levels and values for the calcium-phosphorus ion product both decreased after treatment with AMG 073. Thus, 8 d of treatment with AMG 073 effectively lowers plasma PTH levels and improves several disturbances in mineral metabolism that have been associated with soft tissue and vascular calcification and with adverse cardiovascular outcomes in patients with end-stage renal disease.