Pain prevalence in patients with chronic kidney disease.

BACKGROUND: The prevalence of pain in patients with chronic kidney diseases (CKD) is not known. In the current study, we aim to determine the prevalence of pain in CKD patients and its associations with various medical and psychosocial factors. METHODS: Consecutive CKD patients who were presented to the renal clinic at Olive View-UCLA Medical Center, a Los Angeles County tertiary referral center, over a 3-month period were interviewed on their medical and psychosocial histories and a history of pain including duration, severity and source. Chi2-testing for independence and binary logistic regression performed for the presence of pain and CKD stages as well as other medical and psychosocial factors were determined. A separate survey for pain was also done for 100 consecutive non-CKD patients who were presented to our ambulatory medicine clinic for routine care. RESULTS: 54.6% of 130 patients with known CKD interviewed were women. Any type of pain of at least a 2 week duration was reported in 72.9%. The most common source of pain was musculoskeletal. The presence of pain of less than a 2 week duration was associated with worse CKD stages (3 - 5 versus 1 - 2) and non-exercisers. Higher body mass index was associated with having pain lasting longer than a 2 week duration. Among patients who had pain, 33.8% used acetaminophen, 15.4% nonsteroidal anti-inflammatory drugs and 7.8% combination analgesics. In contrast to CKD patients, only 9% of non-CKD patients reported to have any type or duration of pain. CONCLUSIONS: Pain was much more prevalent among our CKD compared with non-CKD patients.

The link between lower serum magnesium and kidney function in patients with diabetes mellitus Type 2 deserves a closer look.

INTRODUCTION: We previously reported that lower serum magnesium levels [Mg2+] can be associated with more rapid decline in renal function in patients with diabetes mellitus Type 2 (DM2). We now report long-term renal outcomes of the same patient cohort. MATERIALS AND METHODS: Most recent serum creatinine (SCr) and routine urinary analyses (RUA) for the 550 DM2 patients from our original study were collected. DATA ANALYSIS: Patients with follow-up data were stratified according to the original study: Group 1 had initial [Mg2+] < or = 1.6 - 1.8 mg/dl, Group 3 > 1.8 - 2.0 mg/dl and Group 4 > 2.0 mg/dl. The change in renal function was defined by the ratio of the most recent to the initial SCr as well as slope of 1/SCr-versus-time. Any level of proteinuria detected from RUA provided evidence for overt proteinuria. Renal outcomes were analyzed for each defined patient group. RESULTS: SCr were available for 329 out of 550 patients (59.8%). The duration of follow-up ranged from 93.8 +/- 23.4 - 99.4 +/- 22.4 months among 5 groups. The ratios of the most recent to the initial SCr were 1.54 +/- 1.01, 1.28 +/- 0.51, 1.26 +/- 0.57 and 1.09 +/- 0.29 for Groups 1 - 4, respectively; where the differences between Groups 1, 2 and 3 against Group 4 were significant (p = 0.02, 0.001 and 0.007, respectively). Accordingly, the mean slope of 1/SCr-versus-time was the best for Group 4. RUA were available for 176 patients: 22.2%, 9%, 7.3% and none from Groups 1 to 4, respectively, developed overt proteinuria. CONCLUSION: Our follow-up data suggest a link between low [Mg2+] and worse renal outcomes in DM2 patients.

Death from metastatic donor-derived ovarian cancer in a male kidney transplant recipient.

Posttransplant malignancy developing in an allograft is an uncommon complication of organ transplantation. The tumor may represent malignant transformation of donor or recipient cells that were previously normal, metastatic malignancy of recipient origin or malignancy transmitted from organ donor to recipient. Establishing the origin of the malignancy is critical to treatment algorithms. It is generally believed allograft removal and immunosuppression withdrawal will lead to resolution of transmitted malignancies in cases where the renal allograft is the origin. We report a male patient who developed metastatic ovarian malignancy secondary to donor transmission.

Lower serum magnesium levels are associated with more rapid decline of renal function in patients with diabetes mellitus type 2.

AIMS: Hypomagnesemia has been implicated in adversely affecting diabetic complications. This is a retrospective study designed to determine whether there is any association between serum magnesium concentration [Mg2+] and the rate of renal function deterioration, as determined by the slope of serum creatinine reciprocals versus time (1/SCr-vs-t), in patients with diabetes mellitus type 2 (DM2). MATERIALS AND METHODS: DM2 patients without known kidney disease seen at Olive View-UCLA Medical Center for any reason during January-March 2001 were included. For each patient, all available data from our electronic database for [Mg2+], hemoglobin A(1C) (HbA(1C), serum creatinine (SCr), lipid profiles, routine urinary analysis, as well as history of hypertension and pharmacy profiles were retrieved. The average of all parameters obtained and linear regression analyses for the slope of 1/SCr-vs-t plot were performed for each patient. Patients were stratified by gender and divided into four groups based on increasing [Mg2+]. Correlations between each parameter including the slope of 1/SCr-vs-t and the four magnesium groups were analyzed. RESULTS: 252 males and 298 females with a mean follow-up of 62.6 +/- 22.5 months were included. Patients belonging to lower [Mg2+] groups for both genders had significantly worse slopes of 1/SCr-vs-t plot independent of the presence of hypertension and use of ACEI/ARB, diuretics, HMG-CoA enzyme inhibitors or aspirin. In a multivariate regression analysis controlling for age, HbA(1C) and various components of the lipid profile, [Mg2+] remained an independent predictor for the slope of 1/SCr-vs-t. A trend for worse proteinuria based on routine urinary analysis was observed among patients belonging to the lowest [Mg2+] group. CONCLUSIONS: Lower [Mg2+] is associated with a faster renal function deterioration rate in DM2 patients.

Review article: current management of renal dysfunction in the cirrhotic patient.

The United Network for Organ Sharing database revealed that over the last 4-5 years, an average of 1800 patients were removed from the cadaveric waiting list annually because of patients' death and an additional 400-500 were removed from the list because of the severity of their illnesses. The pre-transplant evaluation process, therefore, requires careful and continued assessment of the patient's pulmonary, cardiac and renal function among others. This article describes a systematic approach to the evaluation and management of renal dysfunction complicating the course of advanced liver disease, the pathogenic mechanisms and current recommendations for the treatment of hepatorenal syndrome, and the indications for combined liver-kidney transplantation.

Sodium and water disturbances in patients with Sheehan's syndrome.

Sheehan's syndrome has been attributed to ischemic damage of the pituitary gland or hypothalamic-pituitary stalk during the peripartum period. Well-described clinical features of Sheehan's syndrome include hypothyroidism, adrenal insufficiency, hypogonadism, growth hormone deficiency, hypoprolactinemia, and different sodium and water disturbances. The occurrence of sodium and water disturbances associated with Sheehan's syndrome depends on the degree of pituitary damage, time of onset since the initial pituitary insult, and concurrent medical conditions that also may play a role in sodium and water balance. We present a patient with Sheehan's syndrome with severe chronic hyponatremia; discuss a potential problem in the patient's management; and review the literature for various sodium and water disturbances, including acute and chronic hyponatremia as well as overt and subclinical central diabetes insipidus. Although Sheehan's syndrome is more prevalent in developing countries, the increasingly large immigrant population within the United States warrants better awareness of this syndrome and its potential complicating sodium and water disturbances. Prompt diagnosis and an understanding of the pathogenic mechanisms of sodium and water disturbances associated with Sheehan's syndrome may avoid potential treatment-related complications.

Cyclosporine and tacrolimus-associated thrombotic microangiopathy.

The development of thrombotic microangiopathy (TMA) associated with the use of cyclosporine has been well documented. Treatments have included discontinuation or reduction of cyclosporine dose with or without concurrent plasma exchange, plasma infusion, anticoagulation, and intravenous immunoglobulin G infusion. However, for recipients of organ transplantation, removing the inciting agent is not without the attendant risk of precipitating acute rejection and graft loss. The last decade has seen the emergence of tacrolimus as a potent immunosuppressive agent with mechanisms of action virtually identical to those of cyclosporine. As a result, switching to tacrolimus has been reported to be a viable therapeutic option in the setting of cyclosporine-induced TMA. With the more widespread application of tacrolimus in organ transplantation, tacrolimus-associated TMA has also been recognized. However, literature regarding the incidence of the recurrence of TMA in patients exposed sequentially to cyclosporine and tacrolimus is limited. We report a case of a living donor renal transplant recipient who developed cyclosporine-induced TMA that responded to the withdrawal of cyclosporine in conjunction with plasmapheresis and fresh frozen plasma replacement therapy. Introduction of tacrolimus as an alternative immunosuppressive agent resulted in the recurrence of TMA and the subsequent loss of the renal allograft. Patients who are switched from cyclosporine to tacrolimus or vice versa should be closely monitored for the signs and symptoms of recurrent TMA.

Overcorrection of hyponatremia: where do we go wrong?

Predicted sodium concentrations [Na(+)] based on traditional calculations for the correction of hyponatremia often do not match treated [Na(+)], for various reasons. In many situations, hyponatremia is corrected at unexpectedly rapid rates. The authors present an analysis of two cases of overly rapid correction of hyponatremia despite apparently appropriate management based on initial evaluations. The mistakes involved are discussed and simple calculations demonstrated to prove that the overcorrections did not occur at random. Overcorrection in one case involved miscommunications between the emergency room and admitting physicians regarding the amount of saline and potassium already administered to the patient. Unexpected hypoosmotic polyuria was responsible for overcorrection in the other case. Overcorrection of hyponatremia may be preventable in many cases. In general, overcorrection of hyponatremia is caused by either "too much salt (Na(+) + K(+)) gained" or "too much water lost." Recognizing common pitfalls will enable physicians to avoid overcorrection and its attendant risk of fatal osmotic demyelinating syndrome (ODS).

Renal abnormalities in sickle cell disease.

Renal abnormalities in sickle cell disease. Sickle cell nephropathy is indicated by sickled erythrocytes, with the consequent effects of decreased medullary blood flow, ischemia, microinfarct and papillary necrosis. Impaired urinary concentrating ability, renal acidification, hematuria, and potassium secretion are also found. There may be a causal relationship between an increase in nitric oxide synthesis and experimental sickle cell nephropathy, and some studies have indicated that the progression of sickle cell nephropathy is hemodynamically mediated. Although there are many studies showing that proteinuria, nephrotic syndrome, chronic progressive renal failure, and acute renal failure syndromes are the outcome of this disease, the pathogenic mechanism(s) and potential therapies remain to be elucidated. Survival of patients with sickle cell nephropathy who progress to end-stage renal disease (ESRD) is equal to non-diabetic ESRD patients, and graft survival rates are also similar for those who undergo renal transplantation. This article presents a historical review of the glomerular and tubular disorders associated with sickle cell nephropathy, and reviews therapeutic indications to slow its progression. Further research is needed.

The kidney in liver transplantation.

Early recognition and determination of the cause of renal failure in patients with ESLD can be difficult because of the potential interplay among various factors and the wide array of differential diagnoses. A systematic approach, however, assists clinicians to identify common and potentially reversible causes of ARF. It is crucial to distinguish patients with functional renal failure, such as HRS, from those with advanced irreversible renal disease. Isolated liver transplantation is the treatment of choice for the former, and CLKT may be a therapeutic option for the latter. Because of the ever-increasing shortage of donor organs, CLKT must be used judiciously. Kidney biopsy may resolve diagnostic dilemmas. Management of renal complications post-OLT remains a challenge for the physician caring for transplant patients. Modification of nephrotoxic immunosuppressive regimens to avoid postoperative ARF/CRI has met with variable results. Azathioprine has been used in place of cyclosporine. Therapy with polyclonal antilymphocyte preparations or anti-OKT3 monoclonal antibodies (Orthoclone) should be reserved for patients with delayed graft function and for the treatment of acute rejection. The routine use of these agents as prophylactic therapy is not recommended. Data on the impact of renal insufficiency on patient and allograft outcome are inconsistent. Nonetheless, the authors' literature review suggests that renal failure associated with sepsis and, except for patients with HRS, renal failure requiring dialysis are the most consistent features associated with a worse outcome. The need for preoperative or postoperative dialysis has no adverse effect on survival in patients with HRS. On long-term follow-up, despite a greater percentage of patients reaching ESRD in patients with HRS compared with their non-HRS counterparts, the overall outcome in patients with HRS following OLT is favorable. In patients with HRS requiring prolonged dialysis (i.e., greater than 4 weeks), however, irreversible renal failure may develop, necessitating CLKT. Ideally, timely referral of patients for OLT may avoid this complication and obviate the need for double organ transplantation.

N-methyl-D-aspartate receptors mediate hypoxic neuronal injury in cortical culture.

The ability of several glutamate receptor antagonists to reduce hypoxic cortical neuronal injury was quantitatively examined in cell cultures derived from fetal mice. Cultures exposed to hypoxia for 8 hr showed by the following day widespread neuronal injury, which was substantially attenuated by addition of the specific N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (APV). The protective effect of APV was concentration dependent (ED50 about 2 microM) and stereospecific (D-APV approximately 100 times more potent that L-APV). Neuron-protective effects were also observed with several other NMDA antagonists: 2-amino-7-phosphonoheptanoate, phencyclidine and (+)-SKF 10,047 [(+)-N-allylnormetazocine]--as well as with the nonspecific glutamate antagonists D-glutamylglycine and kynurenate. In addition, a similar antagonist profile was observed with a chemical model of hypoxic neuronal injury, produced by brief exposure to high concentrations of cyanide. In contrast, 1 mM concentrations of glutamate diethylester and gamma-aminomethyl sulfonate, compounds reported in some studies to preferentially antagonize non-NMDA glutamate receptors, failed to protect neurons against either hypoxia or cyanide. These results are consistent with the hypothesis that NMDA receptors are preferentially involved in the pathogenesis of hypoxic cortical neuronal injury and suggest that cortical cell culture may be a useful system in which to quantitatively characterize the pharmacology of that injury.

Dextrorphan and dextromethorphan attenuate hypoxic injury in neuronal culture.

The dextrorotatory opioid derivatives, dextrorphan and dextromethorphan, can attenuate hypoxic injury in cortical cell cultures. This effect is concentration-dependent in the micromolar range, and not strongly stereospecific, as it can also be demonstrated with the levorotatory enantiomer of dextrorphan, levorphanol. The possibility that these clinically available compounds may have therapeutic utility in hypoxic or ischemic encephalopathy warrants further investigation.