Prerenal Azotemia Research Articles

Evolving Practices in Critical Care and Potential Implications for Management of Acute Kidney Injury

Acute kidney injury (AKI) is a common complication in hospitalized patients, with an incidence of 3 to 10% (1–4). In-hospital mortality rates that are associated with AKI remain high, in the range of 30 to 70% (5–8), despite significant improvements in dialytic technology as well as important advances in critical care, which have resulted in improved survival for other critical illnesses, including acute lung injury and sepsis (9). These improvements include continuous renal replacement therapies, which allow for continuous removal of solutes and fluid and may be tolerated better from a hemodynamic standpoint, and biocompatible dialysis membranes, which are associated with reduced complement and granulocyte activation. In general, indications for dialysis in the acute care setting have been extrapolated from those that are applied in chronic kidney disease, including volume overload that is refractory to diuretic therapy; electrolyte abnormalities (in particular hyperkalemia); uremic complications (pericarditis or pleuritis); severe acidosis (pH < 7.20); and selected toxic ingestions, such as methanol, ethylene glycol, and other water-soluble agents (10,11). However, the evidence base supporting specific dialysis practices in the acute care setting is limited. For example, several studies that were completed in the 1960s and 1970s compared “early” and “late” initiation of dialysis, using blood urea nitrogen (BUN) to define early and late (Table 1). These studies primarily were cohort studies that used historical controls, not randomized, clinical trials. The results of these investigations, along with extrapolation from the ESRD population, promoted recent practice patterns. Currently, many nephrologists often delay dialysis in the acute care setting until the patient has an impending complication of AKI, such as hyperkalemia leading to cardiac arrhythmias, acidosis resulting in hypotension, or oliguria leading to volume overload or hypoxemia, or until the BUN exceeds 100 mg/dl (18). Given differences in protein catabolism, …

Pulmonary hypertension and right-sided heart failure in an adult llama with hepatic disease

A 13-year-old llama was examined because of lethargy, inappetence, and syncope. Physical examination revealed muffled heart and lung sounds and peripheral edema. Clinicopathologic abnormalities included lymphopenia, hyperglycemia, prerenal azotemia, mild hyponatremia, mild hypoalbuminemia, and high gamma-glutamyltransferase and creatine kinase activities. On ultrasonography, the liver appeared hyperechoic and ascites and pleural effusion were seen. Echocardiography revealed severe dilatation of the right atrium, right ventricle, and pulmonary artery; severe tricuspid regurgitation; and high right ventricular systolic pressure consistent with right-sided heart failure secondary to pulmonary hypertension. Treatment with furosemide was attempted, but because of failing health, the llama was euthanized 4 weeks later. Macronodular cirrhosis of the liver, glomerulonephritis, and intimal fibrosis and medial hypertrophy of muscular pulmonary arteries were seen on histologic examination of postmortem specimens. Findings in this case were similar to those reported for human patients with portopulmonary hypertension secondary to hepatic cirrhosis. Pulmonary hypertension secondary to hepatic disease should be considered in the differential diagnosis of right-sided heart failure.

Section 11: Evaluation and Management of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

Section 11: Evaluation and Management of Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

Elevated Serum Creatinine and a Normal Urinalysis: A Short Differential Diagnosis in the Etiology of Renal Failure

Objective. The diagnosis of renal failure with a normal urinalysis represents a short differential diagnosis that has not been characterized in the literature. This study was designed to identify the specific disease states that encompass this interesting renal condition. Material. The Regenstrief database, which is an electronic medical record containing inpatient laboratory and other clinical data for patients admitted to Wishard Memorial Hospital, was utilized to provide data for this study. Methods. The database was culled to provide data for hospitalized patients admitted between March 1, 1992, and March 1, 2001, with the concurrent findings of a serum creatinine greater than or equal to 2 mg/dL, a normal urinalysis, and diagnoses of obstructive uropathy, multiple myeloma, prerenal azotemia, hypertensive nephrosclerosis, interstitial nephritis, renal vascular disease, hypokalemic nephropathy, and hypercalcemia, as identified by their corresponding ICD-9 codes. Results. A search of the Regenstrief database yielded a total of 190,343 patient admissions. There were 515 patient admissions with renal failure and a concurrent normal urinalysis. The largest specific diagnostic categories within this group were hypertension and prerenal azotemia. Conclusions. An elevated serum creatinine and normal urinalysis present a short differential for the etiologies of renal failure and include such entities as hypertensive nephrosclerosis, prerenal azotemia, obstructive nephropathy, interstitial nephritis, renal vascular disease, and various electrolyte abnormalities. An awareness of these specific disease states may lead to an earlier diagnosis and more effective treatment of renal failure.

Enterostomy as an adjunct to treatment of intra-abdominal sepsis

In 60 patients a small bowel enterostomy was constructed as part of the treatment of various intra-abdominal infectious and obstructive conditions. Eleven patients (18 per cent) died in the immediate postoperative period from continuing sepsis. In one patient closure of the stoma was not considered because of disseminated malignancy. In the remaining 48 patients continuity of the gut was subsequently restored. In 22 patients (46 per cent) complications occurred, 12 (25 per cent) of which were intra-abdominal septic complications. The occurrence of intra-abdominal complications was found to be linked to premature (i.e. within 3 months) closure of the stoma. Reasons for premature closure were stomal difficulties and prerenal azotaemia. Stomal closure was attended by a 10 per cent mortality rate.

The Role of Ultrasound in Renal Insufficiency

Sonography is the best screening modality to evaluate patients presenting with renal insufficiency. Ultrasound findings can be normal in patients with renal disease, especially in prerenal azotemia and acute parenchymal renal disease. Echogenic kidneys indicate the presence of parenchymal renal disease; the kidneys may be of a normal size or enlarged. Small kidneys suggest advanced stage chronic kidney disease. Uncommonly, cystic disease of the kidney, especially adult type polycystic kidney disease may be the cause of the patient's renal insufficiency with bilaterally enlarged kidneys containing multiple cysts of various sizes. If hydronephrosis is present, the level and cause of the obstruction should be sought. When ultrasound cannot diagnose the level and cause of obstruction, other imaging modalities, including CT and MRI may be useful. When renovascular disease (arterial stenosis or venous thrombosis) is suspected, spectral and color Doppler can be useful in detecting abnormalities.

Delayed Small Bowel Obstruction after Blunt Abdominal Trauma

Blunt abdominal trauma may produce acute intra-peritoneal injury requiring laparotomy for intestinal perforation or vascular compromise. Intra-abdominal pathology from blunt trauma may be delayed. Delayed small bowel obstruction after blunt abdominal trauma is a rare clinical entity whose pathogenesis has not been clearly established. We present a case of delayed small bowel obstruction due to stricture formation in the distal duodenum over the spine. The patient is a 56 year-old female who presented to the emergency room with a 5 day history of nausea and vomiting. Initial laboratory testing revealed only pre-renal azotemia consistent with dehydration from persistent vomiting. An abdominal computed tomographic scan was obtained which revealed a distal duodenal obstruction of unclear etiology. There was marked dilatation of the stomach and duodenum. An enteroscopy was performed, which demonstrated a large amount of fluid in the stomach and duodenum with normal-appearing mucosa. However the enteroscope could not be passed beyond the distal duodenum due to extrinsic compression. The duodenal mucosa was normal. A small bowel series was then performed. The stricture in the distal duodenum was 2 cm in length and exhibited delayed passage of contrast. After no improvement with one week of nasogastric suction, the patient was referred for surgery. At laparotomy, over the spine, there was circumferential fibrosis of the duodenum at the junction with the jejunum. Due to the location of the stricture with adjacent vasculature, a gastro-jejunostomy was performed. This case demonstrates the rare entity of post-traumatic delayed small bowel obstruction. The location of the delayed obstruction over the spine in a thin woman suggests a similar anatomic risk as seen in patients with traumatic pancreatitis. Whereas a ductal disruption occurs in traumatic pancreatitis, an inflammatory process related to the blunt trauma over the spine may result in fibrosis and progressive narrowing of the bowel. Clinicians should be aware of delayed post-traumatic obstruction and focus the evaluation of the bowel to that overlying the spine.

Drug-induced nephropathy: an update

Medications cause renal disease by promoting various types of injury in the kidney. Several drugs reduce renal perfusion and cause prerenal azotemia. Vascular disease can develop following exposure to various medications through direct and indirect effects. A number of glomerular lesions have been described with therapeutic agents and illicit drugs. Acute interstitial nephritis occurs from a drug-induced allergic reaction, which promotes interstitial inflammation and tubular damage. Acute tubular necrosis is a dose-dependent process that occurs from direct drug toxicity on tubular epithelia. Other less common patterns of drug-induced tubular injury include osmotic nephropathy, crystal nephropathy and acute nephrocalcinosis. Finally, postrenal azotemia from structural or functional obstruction of the urinary tract also complicates therapy with a number of medications.

Feasibility of hand-assisted laparoscopic surgery (HALS) in gynecologic oncology patients

5153 Objective: Although hand-assisted laparoscopic surgery (HALS) has been utilized in multiple surgical procedures, limited data exists on the use of HALS for gynecologic oncology indications. Our goal was to evaluate the indications, potential benefits, and complications of HALS in cases of suspected gynecologic malignancy. Methods: We performed a retrospective chart review of patients who had an HALS procedure performed from 1/03 until 10/04. Data was collected on patient demographics, indications for surgery, operative morbidity, and length of stay. Results: 37 patients who underwent a HALS procedure were identified. The median age was 51 years (range, 19–86) and the mean BMI was 28.7 m2 (range, 17.8–40.7). The indications for surgery included pelvic mass (n=29), prophylactic oophorectomy (n=2), secondary cytoreduction for ovarian cancer (n=2), uterine fibroids (n=2), surgical staging for endometrial cancer (n=1), post-menopausal bleeding (n=1), and vaginal vault prolapse (n=1). The mean estimated size of pelvic mass removed was 11.2 cm (range, 3–30). 6 of 29 (21%) patients with a pelvic mass were diagnosed with an ovarian carcinoma. All patients underwent general endotracheal anesthesia for the following procedures performed: oophorectomy (n=31), lysis of adhesions (n=14), surgical staging (n=9), hysterectomy (n=9), loop colostomy (n=1), and sacrocolpo suspension (n=1). Mean operating time was 90 minutes (range, 46–157) with mean estimated blood loss of 110 cc (range, 10–400). One patient was converted to laparotomy due to a large unresectable mass. One intraoperative complication of epigastric vessel injury due to trocar placement occurred. The average length of post-operative hospital stay was 2.8 days (range, 2–5). 4 of 37 (11%) patients experienced a post-operative complication including ileus (n=2), pre-renal azotemia (n=1), and transfusion of packed red blood cells (n=1). Conclusions: HALS is an innovative surgical technique that allows a number of surgical procedures to be accomplished in gynecologic oncology patients. HALS appears to be safe and feasible based on acceptable operating time, estimated blood loss, conversion rate, complication rate, and length of hospital stay. No significant financial relationships to disclose.

Dendrimer-enhanced MRI as a diagnostic and prognostic biomarker of sepsis-induced acute renal failure in aged mice

Acute renal failure (ARF) induced by sepsis has a high mortality. In an aged mouse model of sepsis-induced ARF we have previously shown that renal injury occurs before serum creatinine is elevated. Development of a noninvasive biomarker that could diagnose renal dysfunction early in sepsis and monitor the response to therapy would be very valuable. We performed magnetic resonance imaging (MRI) with gadolinium-based G4 dendrimer intravenous contrast in a fluid- and antibiotic-treated cecal ligation and puncture (CLP) sepsis model in aged mice. Imaging was also performed in a mouse volume depletion model and in models of ARF induced by ischemia/reperfusion (I/R) and cisplatin. Twenty hours post-CLP, aged mice had a distinct pattern of renal injury using dendrimer-enhanced MRI. This pattern was different from renal injury induced by either cisplatin or I/R. Prerenal azotemia induced by volume depletion was distinguished from sepsis by dendrimer-enhanced MRI. Dendrimer-enhanced MRI detected renal dysfunction 6 hours post-CLP, a time when serum creatinine was still normal. Ethyl pyruvate reversed the renal dysfunction detected by dendrimer-enhanced MRI at 20 hours, but not at 6 hours post-CLP. The appearance of renal dysfunction on dendrimer-enhanced MRI at 6 hours post-CLP predicted the length of survival. Dendrimer-enhanced MRI is a novel biomarker that provides information for the early diagnosis, drug responsiveness, and prognosis of sepsis-induced ARF.

Celecoxib associated with lower rate of renal dysfunction compared to nonspecific inhibitor NSAIDs

Both the COX-1 and COX-2 isoforms are expressed by the human kidney and vasculature. Therefore, it is important to evaluate the renovascular effects of COX-2 specific inhibitors and NSAIDs, particularly in patients with preexisting renal dysfunction. The Celecoxib Long-term Arthritis Safety Study (CLASS) assessed gastrointestinal outcomes associated with supratherapeutic doses of the COX-2 specific inhibitor celecoxib (400mg bid), and standard doses of NSAIDs, ibuprofen (800mg tid) and diclofenac (75mg bid), in patients with rheumatoid arthritis (RA) or osteoarthritis (OA). The trial's full database provided a large cardiorenal database for studying renal-related adverse events associated with nonspecific NSAIDs and celecoxib. Complete methods and gastrointestinal and cardiovascular results are published elsewhere. Enrolled patients had a serum creatinine ≤1.5mg/dL reflecting normal renal function. Renal function was assessed in all patients including those with mild prerenal azotemia defined by a baseline blood urea nitrogen (BUN) level of >20mg/dL. The renovascular effects measured in these patients were clinically important reductions in renal function (defined as an increase in serum creatinine >0.5mg/dL from baseline) and mean serum creatinine/estimated creatinine clearance. In patients with mild prerenal azotemia significantly fewer patients taking celecoxib exhibited clinically important reductions in renal function (3.4%) compared with either diclofenac (8.3%;P ≤0.05) or ibuprofen (7.7%;P ≤0.05). In patients with mild renal compromise, celecoxib was associated with a significantly lower rate of renal dysfunction at supratherapeutic doses compared with diclofenac and ibuprofen at standard doses. These data suggest that celecoxib may be a more suitable alternative to treat chronic pain and inflammation than nonspecific NSAIDs in patients with compromised renovascular function. (See Table) *P ≤ 0.05; ANCOVA, Fisher's exact test *P ≤ 0.05; ANCOVA, Fisher's exact test

Acute Renal Failure in a Tertiary Care Center in Nepal

From July 1998 to July 1999, 45 cases of acute renal failure were treated at Bir Hospital, Kathmandu. Out of which 24 were male and 21 were female. Age ranged from 11 months to 84 years with mean age being 35 years and 9 cases were below 10 years. Four cases with pre-renal azotaemia and twenty five cases of acute tubular necrosis (ATN) accounted for 64% of all cases. These were due to gastroenteritis 10, sepsis 6, post surgical 1, trauma 1 and obstretical complications 5. Multiple hornet stings were responsible for acute renal failure in 3 cases, acute urate nephropathy in 1 case and miscellaneous causes in 2 cases. Glomerulonephritis / vasculitis accounted for 17.7%, acute interstitial nephritis 4.4%, haemotytic uraemic syndrome (HUS) 6.6%, and post renal azotaemia in 6.6% of all cases. Mean serum creatinine was 8 mg/dl, mean blood urea 190 mg/dl. Eight cases were treated only conservatively, eighteen received haemodialysis, fourteen received peritoneal dialysis, three received both and two refused for dialysis. Average duration of hospital stay was 13.6 days. Out of the forty-five cases twenty-nine recovered normal renal function, ten expired, two recovered partially, two progressed to chronic renal failure and two left against medical advice. Overall mortality was 22.2%. Common causes of acute renal failure in our setting were gastroenteritis (22%) and sepsis (20%). HUS was exclusively seen in children following bacillary dysentery. Multiple hornet stings is an important cause of acute renal failure in our country.

Recurrent Severe Aseptic Meningitis after Exposure to Lamotrigine in a Patient with Systemic Lupus Erythematosus

Recurrent Severe Aseptic Meningitis after Exposure to Lamotrigine in a Patient with Systemic Lupus Erythematosus

Ethylene Glycol intoxication with and without simultaneous diabetic ketoacidosis: A report of nine cases and review of the literature

Objective: To describe the clinical and biochemical observations made on nine patients with ethylene glycol intoxication(EGI) of whom five presented with simultaneous diabetic ketoacidosis (DKA). Methods: A retrospective chart search fordischarge diagnosis including the term ethylene glycol intoxication was conducted at University Hospitals of ClevelandInformation Services (Cleveland, OH) from 1986 through 1998. Nine (N=9) patients were identified and subsequentlydivided into two Groups (A & B). Group A included 5 patients with both DKA and EGI. Group B included 4 patients withEGI without DKA. Clinical manifestations and laboratory tests are summarized for both Groups. Serum specimens for allpatients were analyzed for ethylene glycol, propylene glycol, methanol, serum ketones, glucose, pH, electrolytes, liver andkidney function tests, lipase, amylase, cholesterol, triglycerides, C-peptide and glycosylated Hb. Results: Group A patientspresented with more severe hyperglycaemia accompanied by increased insulin requirements, glucose toxicity, more severeosmotic diuresis induced severe dehydration, pre-renal azotemia, transient rhabdomyolysis and hypertriglyceridaemia. Theiracute renal failure was fully reversible upon discharge. Finally, the length of hospital stay of patients in Group A wassignificantly longer than that of Group B patients, although mortality rate was reduced. Permanent and irreversible kidneydamage requiring haemodialysis was seen in all Group B patients. Conclusions: severe DKA presenting with simultaneoushigh anion and osmolal gap should prompt suspicion to the hypothetical concomitant EGI, particularly in those patients witha history of alcoholism, depression and past suicidal attempts.

Fulminant hepatic failure

Abstract Analysis of the first 150 cases collected from 73 centers reporting to the Fulminant Hepatic Failure Surveillance Study showed that 80 patients had presumable viral hepatitis, of whom 62 died. Of 41 patients who had recent surgery, 36 died. In 35 patients massive liver necrosis developed less than three weeks after halothane anesthesia, and 27 (77 per cent) of these had multiple exposures to halothane. The risk from halothane is small, but this complication was present in nearly one quarter of the cases reported in our study. When the use of halothane is desired, multiple exposure should be avoided, if possible. Moreover, postoperative fever after exposure to halothane, otherwise "unexplained," is an important warning sign, and should be thoroughly investigated and taken into consideration when further exposure to this anesthetic is contemplated. The physician prescribing halothane must balance need against risk.

Biologic markers for the early detection of acute kidney injury

This review discusses the current status of several biomarkers as potential diagnostic tools in patients with acute kidney disease. Although the term "acute renal failure" has generally been used to describe acute kidney dysfunction that runs the spectrum from mild prerenal azotemia with no renal pathologic changes and no functional failure to severe oliguric renal dysfunction associated with tubular necrosis with failure of function, this spectrum is better described by the term "acute kidney injury." The mortality rate of hospitalized patients with severe acute kidney disease has not decreased significantly over the past 50 years despite advances in supportive care. The absence of sensitive and specific biomarkers for detecting injury early, grading the severity of the injury, and monitoring the response to therapy has impaired progress in the field and has had a very detrimental effect on the design and outcome of clinical trials in acute kidney disease. As a result of reliance on serum creatinine as a marker for injury and diagnosis, the institution of therapy is markedly delayed. The search for new biomarkers for acute kidney injury is evolving rapidly with advancement in modern technologies. With better biomarkers we will have the ability to detect injury earlier, identify subclinical injury, provide prognostic information on the course of renal impairment, identify the nephron segments most affected, provide a rationale for segmentation of patients for clinical studies, guide timing of therapy, assess response to therapy, and screen patients at risk for renal injury.

Pass the Salt

Sodium is the most abundant extracellular ion. Historically, therapy with hypertonic saline was widely used for a variety of conditions. Currently, there are 3 primary indications for its use in critical care: hyponatremia, volume resuscitation, and brain injury. SIADH and CSW syndrome may require sodium replacement, but most cases of hyponatremia can be managed without administration of hypertonic saline. Studies of use of hypertonic saline in hypovolemia and brain injury are promising, but additional research is needed to better define optimal dosing regimens and to determine the relative risks associated with hypertonic saline versus conventional treatment for the management of patients with head injuries and for volume resuscitation in shock states.

Renal effects of high-dose celecoxib (CX) and docetaxel (D) During a phase II trial for hormone resistant prostate cancer (HRPC)

4752 Background: Patients with HRPC were treated with D and high doses of the Cox-2 inhibitor, CX. (Kasimis et al; Proc ASCO 2004 subm) Potential adverse renal effects from prostaglandin inhibition include: 1) acute renal failure (ARF) from vasoconstriction; 2) interstitial nephritis +/- nephrotic syndrome; 3) hyperkalemia (*K); 4) increased sodium (Na) and water reabsorption; 5) hypertension (HTN). Methods: 18 patients with HRPC and median age 73.5 years, received a median of 3 cycles (2–6) of D, 30 mg/m2 IV weekly x 3 of each 4 week cycle, and CX 400 mg bid daily . Chemistry and blood pressure data were collected at baseline and then monthly. The repeated measure analysis with General Linear Model (GLM) and multi-level t test comparison were performed. All cases of ARF and *K were evaluated by nephrologists. Results: Serum K was the only variable that showed a significant difference. Compared to baseline, mean serum K was greater in month 2, (p=0.02), but not in other months. None of the following differed significantly from baseline: glomerular filtration rate (GFR) by Cockroft-Gault formula, serum creatinine, urea, Na, chloride, bicarbonate, calcium; fractional excretion of Na (FENa), transtubular potassium gradient (TTKG), urine osmolarity, urinary protein/creatinine ratio (P/C), or BP. There were 5 cases of ARF in 4 patients; causes were prerenal azotemia in 2, obstruction in 2, and contrast in 1. All cases were reversible, and CX treatment was restarted after a short discontinuation. Two patients developed *K, none > 6.0 mmol/l. Conclusions: The incidence of ARF and *K was low, and the causes were attributed to factors other than CX. Mean serum K was increased only transiently. No statistical differences were found in renal function (calculated GFR, serum creatinine) renal tubular handling of Na, K or water (FENa, TTKG, or urine osmolarity, respectively), urine protein excretion, or blood pressure. These results suggest that high dose CX is well tolerated by the kidneys. Supported by Aventis and Pfizer. No significant financial relationships to disclose.

Renal effects of high-dose celecoxib (CX) and docetaxel (D) During a phase II trial for hormone resistant prostate cancer (HRPC)

4752 Background: Patients with HRPC were treated with D and high doses of the Cox-2 inhibitor, CX. (Kasimis et al; Proc ASCO 2004 subm) Potential adverse renal effects from prostaglandin inhibition include: 1) acute renal failure (ARF) from vasoconstriction; 2) interstitial nephritis +/- nephrotic syndrome; 3) hyperkalemia (*K); 4) increased sodium (Na) and water reabsorption; 5) hypertension (HTN). Methods: 18 patients with HRPC and median age 73.5 years, received a median of 3 cycles (2–6) of D, 30 mg/m2 IV weekly x 3 of each 4 week cycle, and CX 400 mg bid daily . Chemistry and blood pressure data were collected at baseline and then monthly. The repeated measure analysis with General Linear Model (GLM) and multi-level t test comparison were performed. All cases of ARF and *K were evaluated by nephrologists. Results: Serum K was the only variable that showed a significant difference. Compared to baseline, mean serum K was greater in month 2, (p=0.02), but not in other months. None of the following differed significantly from baseline: glomerular filtration rate (GFR) by Cockroft-Gault formula, serum creatinine, urea, Na, chloride, bicarbonate, calcium; fractional excretion of Na (FENa), transtubular potassium gradient (TTKG), urine osmolarity, urinary protein/creatinine ratio (P/C), or BP. There were 5 cases of ARF in 4 patients; causes were prerenal azotemia in 2, obstruction in 2, and contrast in 1. All cases were reversible, and CX treatment was restarted after a short discontinuation. Two patients developed *K, none > 6.0 mmol/l. Conclusions: The incidence of ARF and *K was low, and the causes were attributed to factors other than CX. Mean serum K was increased only transiently. No statistical differences were found in renal function (calculated GFR, serum creatinine) renal tubular handling of Na, K or water (FENa, TTKG, or urine osmolarity, respectively), urine protein excretion, or blood pressure. These results suggest that high dose CX is well tolerated by the kidneys. Supported by Aventis and Pfizer. No significant financial relationships to disclose.

Nonimmunologic complications of kidney transplantation

•Lymphoceles may be more common in patients treated with target of rapamycin (TOR) inhibitors •Urine leaks (1% to 3% incidence)•Ureteral obstruction (strictures, ureteral rejection, BK polyoma infection) •Bleeding•Thrombosis (1% to 2% incidence)•Mycotic aneurysms•Late arterial stenosis •Caused by surgery or trauma 1.Valente JF, Schulak JA: Surgical considerations in kidney transplantation, in Hricik DE (ed): Kidney Transplantation: State of the Art. London, UK, Remedica Publishing, 2003, pp 79–962.Langer RM, Kahan BD: Incidence, therapy, and consequences of lymphocele after sirolimus-cyclosporine-prednisone immunosuppression in renal transplant recipients. Transplantation 74:804–808, 2002 •Most common cause of mortality (40% to 50%) after kidney transplantation •Hypertension (≥60% prevalence)•Hyperlipidemia (≥60% prevalence, severity influenced by type of immunosuppression)•Diabetes mellitus/glucose intolerance ▪Worsening glycemic control in previous diabetics▪New-onset diabetes mellitus in 10% of patients (with wide variations depending on risk factors: advanced age, African-American or Hispanic ethnicity, type of immunosuppression)•Smoking•Obesity •Anemia•Role of impaired renal function•Proteinuria•Hyperhomocysteinemia 1.Kasiske BL: Epidemiology of cardiovascular disease after kidney transplantation. Transplantation 72:S5-S8, 2001 (suppl 6)2.Woodward RS, Schnitzler MA, Baty J, et al: Incidence and cost of new onset diabetes mellitus among U.S. waitlisted and transplanted renal allograft recipients. Am J Transplant 3:590–598, 20033.Meier-Kriesch HU, Arndorfer JA, Kaplan B: The impact of body mass index on renal transplant outcomes: A significant independent risk factor for graft failure and patient death. Transplantation 73:70–74, 20024.Djamali A, Becker YT, Simmons WD, Johnson CA, Premasathian N, Becker BN: Increasing hematocrit reduces early posttransplant cardiovascular risk in diabetic transplant recipients. Transplantation 76:816–820, 20035.Meier-Kriesch HU, Baliga R, Kaplan B: Decreased renal function is a strong risk factor for cardiovascular death after renal transplantation. Transplantation 75:1291–1295, 2003 •Herpes viruses: ▪Cytomegalovirus ○Prophylaxis and treatment regimens▪Herpes simplex ○Herpes zoster•Hepatitis B and C•Emerging viruses: ▪BK polyoma, Parvovirus, West Nile virus •Prophylaxis and treatment regimens 1.Rubin R: Temporal aspects of transplant infectious disease. Transpl Infect Dis 5:63–64, 20032.Fishman J: Prevention of CMV in transplant patients. Transpl Infect Dis 1:35–39, 1999 (suppl 1)3.Myonakis E, Goes N, Rubin RH, Cosimi AB, Colvin RB, Fishman J: BK virus in solid organ transplantation: An emerging syndrome. Transplantation 72:1587–1592, 20014.Fishman J, Rubin RH, Koziel MJ, Periera BJ: Hepatitis C virus and organ transplantation. Transplantation 62:147–154, 1996 •Incidence varies widely from center to center•Immune and nonimmune mechanisms •Immune causes (cellular versus humoral acute rejection)•Nonimmune causes: ▪Prerenal azotemia▪Calcineurin inhibitor nephrotoxicity▪Obstructive uropathy▪Hemolytic uremic syndrome (secondary to calcineurin inhibitors)▪Vascular obstruction •Chronic allograft nephropathy ▪Immune mechanisms (role of humoral immunity and indirect allopeptide recognition)▪Nonimmune mechanisms (drug nephrotoxicity, effects of hypertension and hyperlipidemia, ischemia-reperfusion injury, viral infection)•Recurrence of native kidney disease•De novo kidney disease (eg, membranous nephropathy, diabetic nephropathy) 1.Burdmann EA, Andoh TF, Yu L, Bennett WM: Cyclosporine nephrotoxicity. Semin Nephrol 23:465–476, 20032.Waaga AM, Gasser M, Laskowski I, Tilney NL: Mechanisms of chronic rejection. Curr Opin Immunol 12:517–521, 20003.Ramos EL, Tisher CC: Recurrent diseases in the kidney transplant. Am J Kidney Dis 24:142–154, 1994 Neoplastic disorders occurring with higher frequency than in the general population •Role of Epstein-Barr virus •Increased incidence with time posttransplantation•Relatively high ratio of squamous to basal cell carcinoma •Cervical and vulvar carcinoma•Kaposi’s sarcoma Influence of Immunosuppressive Drugs on the Metastatic Potential of Solid Tumors 1.Penn I: Cancers in renal transplant recipients. Adv Ren Replace Ther 7:147–156, 20002.Dampanich E, Kasiske BL: Risk factors for cancer in renal transplant recipients. Transplantation 68:1859–1864, 1999 •High fracture incidence after transplantation ▪Underlying renal osteodystrophy▪Persistent hyperparathyroidism▪Hypogonadism▪Drug-induced osteopenia (corticosteroids, calcineurin inhibitors) Aseptic Necrosis 1.Shane E, Epstein S: Transplantation osteoporosis. Transplant Rev 15:11–32, 2001 •Pharmacokinetic or pharmacodynamic •Antiproliferative agents •Cushingoid features with corticosteroids, hirsutism and gingival hyperplasia with cyclosporine, alopecia with tacrolimus and antiproliferative agents •Corticosteroid-induced acne and ecchymoses •Corticosteroids, antiproliferative agents •Hyperkalemia, hypomagnesemia associated with calcineurin inhibitors; sodium retention associated with corticosteroids and calcineurin inhibitors •Calcineurin inhibitors 1.Danovitch GM: Immunosuppressive medications and protocols for kidney transplantation, in Danovitch GM (ed): Handbook of Kidney Transplantation. (ed 3). Philadelphia, PA, Lippincott Williams & Wilkins, 2001, pp 62–110