Post-renal transplantation hypophosphatemia

An understanding of the pathophysiologic mechanisms of post-renal transplant (PRT) bone disease is of important clinical significance. Although bone disease occurs after all solid organ transplantation, the cumulative skeletal fracture rate remains high in PRT subjects while reaching a plateau with other transplantations. One major difference in the pathophysiology of PRT bone disease is, perhaps, due to persistent renal phosphorus (Pi) wasting. Novel phosphaturic agents have recently been suggested to participate in the development of bone disease in PRT subjects. However, it is unclear as of yet whether these factors alone or in conjunction with excess parathyroid hormone (PTH) secretion play a key role in the development of negative Pi balance and consequent bone disease in this population. In this review, I present a natural history of PRT hypophosphatemia and persistent renal Pi leak, provide pathophysiologic insight into these developments, and discuss the difficulty in diagnosing these phenotypes in both adult and pediatric populations.     

Post-renal transplantation hypophosphatemia: a review and novel insights

PURPOSE OF REVIEW: This review intends to elucidate the pathophysiologic mechanism of renal phosphorus loss in the post-renal transplantation population. This review will provide new insight in to the pathophysiologic mechanism(s) responsible for the development of this phenomenon and will also explore the pathogenetic role of persistent phosphorus wasting in the development of post-renal transplantation osteodystrophy. RECENT FINDINGS: Recently, the phosphaturic hormone, fibroblast growth factor-23, has been ascertain to be increased in the sera of patients with chronic kidney and end-stage renal disease. There is new evidence that a non-PTH humoral factor is persistently present in post-renal transplantation patients that is likely responsible for the observed persistent renal phosphorus loss. We offer that fibroblast growth factor-23 (and/or other phosphatonins) is the culprit factor responsible for the phenomenon of persistent hypophosphatemia in post-renal transplantation patients. Moreover, we believe that the phenomenon of persistent renal phosphorus wasting is an important but overlooked cause of osteodystrophy and increased fracture risk in this patient population. SUMMARY: The pathophysiology of post-renal transplantation phosphorus wasting is complex and to date is still not fully recognized. Further studies of the regulatory mechanism of fibroblast growth factor-23 and its metabolism may offer additional insights into phosphorus homeostasis and its clinical application in the post-renal transplantation population.     

Post-renal transplantation weight gain: its causes and its consequences

OBJECTIVE: A tendency to increased body mass index (BMI) occurs after renal transplantation. The objective of this study was to analyze the causes and consequences of this weight gain. METHODS: Two hundred twelve renal transplant recipients were divided into 3 groups according to the evolution of their BMI: BMI loss (group 1); BMI increase <10% (group 2); and BMI increase >10% (group 3). RESULTS: The mean BMI gain was 6.2%, weight gain was 3.9 kg, and BMI gain was 1.4 kg/m(2). The patients in group 3 were younger, but there were no other significant differences in gender, preoperative diabetes, acute rejection, or prior BMI. Blood pressure was similar in all 3 groups, but more group 3 patients needed antihypertensive treatment. A progressive increase in total and low-density lipoprotein (LDL)-cholesterol was also observed as patients showed increased BMI. No differences were observed regarding carbohydrate metabolism. Groups 1 and 3 showed a more unfavorable micro-inflammatory profile. The creatinine clearance level was better in group 3 compared with group 1. We found no differences regarding the number of nonfatal postoperative cardiovascular events.     

Clinical manifestations of hypercalcemia and hypophosphatemia after kidney transplantation

Introduction

Abnormalities of calcium and phosphorus metabolism in end-stage renal disease patients can persist after transplantation. We investigated their natural courses after transplantation, their risk factors for posttransplantation hypercalcemia and hypophosphatemia, and their impacts on allograft outcomes.

Methods

We retrospectively analyzed a total of 490 adult patients who underwent kidney transplantations between 2000 and 2009.

Results

The serum calcium continued to increase, and reaching a plateau at around 3 months after transplantation. Thereafter it decreased, reaching a stable level by 2 years. Forty-four patients (9.0%) displayed hypercalcemia within 1 year; it persisted longer than that in 23 subjects (4.7%). Both longer dialysis duration (odds ratio [OR] 1.423; 95% confidence interval [CI], 1.192-1.699) and high intact serum parathyroid hormone (iPTH) level before transplantation (OR 1.002; 95% CI, 1.000-1.003) increased the risk for posttransplantation hypercalcemia. After a significant decrease during the first week, the serum phosphorus level increased, becoming stable between 1 and 6 months after transplantation. Hypophsphatemia occurred in 379 patients (77.3%) with 336 patients displaying hypophosphatemia without hypercalcemia. However, neither hypercalcemia nor hypophosphatemia influenced graft outcomes. Eight patients underwent pretransplantation parathyroidectomy, whereas 4 patients underwent posttransplantation parathyroidectomy. Neither group of patients experienced posttransplantation hypercalcemia.

Conclusions

Both hypercalcemia and hypophosphatemia are common after renal transplantation, especially among patients with a long history of dialysis before transplantation. Strict control of hyperparathyroidism including parathyroidectomy before transplantation may be the appropriate approach to these abnormalities.     

Post-renal transplant erythrocytosis in a child

We report the case of a 7-year-old boy who developed severe erythrocytosis 4 months after successful kidney transplantation, with a well-functioning graft. When the haematocrit rose above 60%, phlebotomy had to be performed once to twice a week in order to keep the haematocrit below 50%. A 3-month course of theophylline therapy did not influence the erythrocytosis significantly. There were 5 further patients with erythrocytosis out of 186 children who had undergone kidney transplantation at our centre.     

Post-renal transplant diabetes mellitus--a retrospective study.

The prevalence of post-transplant diabetes mellitus in 222 consecutive live related renal allograft recipients over a 3-year period was found to be 11.7%. Most of them (20 of 26) developed diabetes mellitus within the first 4 months of transplantation. Post-transplant diabetic patients were older, and had a significantly greater incidence of avascular necrosis of bone. An assessment of risk factors showed that abnormal postprandial blood sugar pretransplant was a significant predictor for development of post-transplant diabetes, whereas cumulative oral steroid dose, weight gain after transplant, type of immunosuppression employed, and graft function were not important. We conclude that post-transplant diabetes mellitus frequently develops in patients with a predisposition by virtue of older age and pretransplant postprandial hyperglycaemia. While steroids are important in the pathogenesis, there was no demonstrable dose-response relationship; post-transplant diabetic patients may be a group with a greater propensity to steroid-induced complications.     

Post-renal transplant calciphylaxis: successful treatment with parathyroidectomy

Calciphylaxis occurs in renal transplant patients more frequently than in chronic hemodialysis patients. It can occur in a patient with normal renal function who is also normocalcemic. Early parathyroidectomy can lead to healing of the skin lesions and prevent death of sepsis.     

Elevated fibroblast growth factor 23 levels as a cause of early post-renal transplantation hypophosphatemia

Background

Hypophosphatemia is a common complication after renal transplantation. Hyperparathyroidism has long been thought to be the cause, but hypophosphatemia can persist after high parathyroid hormone (PTH) levels normalize. Furthermore, calcitriol levels remain inappropriately low after transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast growth factor 23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis, and accumulates in chronic kidney disease. We performed prospective study to investigate if FGF-23 early after renal transplantation contributes to hypophosphatemia.

Methods

We measured FGF-23 levels before and at 1, 2, 4, and 12 weeks after transplantation in 20 renal transplant recipients. Serum creatinine, calcium (Ca), phosphate (Pi), intact PTH (PTH), and 1,25-dihydroxy vitamin D (1,25(OH)₂VitD) were measured at the same time.

Results

FGF-23 levels decreased by 97% at 4 weeks after renal transplantation (PRT) (7,471 ± 11,746 vs 225 ± 295 pg/mL; P < .05) but were still above normal. PTH and Pi levels also decreased significantly after renal transplantation, and Ca and 1,25(OH)₂VitD slightly increased. PRT hypophosphatemia of <2.5 mg/dL developed in 15 (75%) and 12 (60%) patients at 4 weeks and 12 weeks respectively. Compared with nonhypophosphatemic patients, the levels of FGF-23 of hypophosphatemic patients were higher (303 ± 311 vs 10 ± 6.9 pg/mL; P = .02) at 4 weeks PRT. FGF-23 levels were inversely correlated with Pi (r² = 0.406; P = .011); PTH was not independently associated with Pi (r² = 0.132; P = .151).

Conclusions

FGF-23 levels decrease dramatically after renal transplantation. During the early PRT period, Pi rapidly decreased, suggesting that FGF-23 is cleared by the kidney, but residual FGF-23 may contribute to the PRT hypophosphatemia. FGF-23, but not PTH levels, was independently associated with PRT hypophosphatemia.     

Post-renal transplant cytomegalovirus infection: study of risk factors

Objectives

Cytomegalovirus (CMV) is a common opportunistic infection following renal transplantation (RTx). It responds promptly to antiviral treatment. The mortality rate reaches 90% if untreated. Identification of risk factors helps in the early diagnosis of CMV. We studied demographic features, risk factors, and outcomes associated with CMV infection in RTx recipients despite ganciclovir prophylaxis.

Materials and methods

We reviewed 720 RTx recipients between 2007 and 2009. We examined the serostatus of the donor and recipient before transplantation using an enzyme-linked immunosorbent assay, and diagnosed CMV infections in recipients by CMV DNA detection with a polymerase chain reaction.

Results

A total of 42 of 750 (5.6%) patients were identified to display CMV infection (69.1%) or disease (30.9%). Their mean age was 34 ± 13.5 years, with 80.9% men. CMV serologic status was D+/R− in 21.4% and D+/R+ in 59.5% patients. Fever, malaise (76.2%), and leukopenia (52.3%) were the commonest presenting symptoms; diabetes (30.9%) and hepatitis C virus (28.6%) the commonest comorbid conditions. Risk factors were triple drug immunosuppression (47.6%), antithymocyte globulin ATG induction (54.8%), and a rejection episode (26.1%) and methylprednisolone (76.2%) which were more common in CMV disease than infection. Mean CMV DNA at diagnosis was 78,803; 71.2% patients developed CMV within 6 months posttransplantation, the majority occurring after 3 months. With a mean follow-up of 4 ± 1.9 years, patient and graft survival rates were 85.7% and 81% with a mean serum creatinine value of 1.83 ± 12 mg/dL.

Conclusions

Universal CMV prophylaxis was associated with a low incidence (5.6%) and mild form of CMV disease among our patients.     

Perioperative hypophosphatemia in general surgery

Blood phosphorus was measured in consecutive 136 admitted patients in the department of general surgery between Oct. 1987 and Jan. 1988. It was found that 32 cases (23.5%) were with hypophosphatemia on perioperative period. Sixteen patients with normal preoperative blood phosphorus level undergoing digestive tract surgery were randomly divided into 3 groups, each was fasted for 7 days postoperation and given different kind of transfusions. Group 1, patients were given 250 g of glucose daily with no phosphorus, blood phosphorus level was significantly decreased. Group 2, 250 g of glucose with 7.5 mmol of phosphate daily, blood phosphorus level decreased slightly on the 2nd-4th day and returned back to normal on day 7. Group 3,500 g of glucose with 15 mmol of phosphate daily, blood phosphorus level decreased moderately on the 2nd-4th day, and returned to normal level on day 7. Perioperative hypophosphatemia was attributed to: (1) Poor absorption or massive loss of phosphorus through digestive tract. (2) Intracellular transferring of blood phosphorus accompanied by the phosphorylation of saccharide. (3) Excessive excretion of phosphorus through urine. The authors suggested that 7-9 mmol of phosphates per 100 kcal daily for the prevention and 7-15 mmol of phosphates per 1000 kcal daily for the treatment of hypophosphatemia.     

Approach to treatment of hypophosphatemia

Hypophosphatemia can be acute or chronic. Acute hypophosphatemia with phosphate depletion is common in the hospital setting and results in significant morbidity and mortality. Chronic hypophosphatemia, often associated with genetic or acquired renal phosphate-wasting disorders, usually produces abnormal growth and rickets in children and osteomalacia in adults. Acute hypophosphatemia may be mild (phosphorus level, 2-2.5 mg/dL), moderate (1-1.9 mg/dL), or severe (<1 mg/dL) and commonly occurs in clinical settings such as refeeding, alcoholism, diabetic ketoacidosis, malnutrition/starvation, and after surgery (particularly after partial hepatectomy) and in the intensive care unit. Phosphate replacement can be given either orally, intravenously, intradialytically, or in total parenteral nutrition solutions. The rate and amount of replacement are empirically determined, and several algorithms are available. Treatment is tailored to symptoms, severity, anticipated duration of illness, and presence of comorbid conditions, such as kidney failure, volume overload, hypo- or hypercalcemia, hypo- or hyperkalemia, and acid-base status. Mild/moderate acute hypophosphatemia usually can be corrected with increased dietary phosphate or oral supplementation, but intravenous replacement generally is needed when significant comorbid conditions or severe hypophosphatemia with phosphate depletion exist. In chronic hypophosphatemia, standard treatment includes oral phosphate supplementation and active vitamin D. Future treatment for specific disorders associated with chronic hypophosphatemia may include cinacalcet, calcitonin, or dypyrimadole.     

Severe hypophosphatemia after head injury

Hypophosphatemia occurs in a variety of clinical conditions. It develops in parallel with phosphate depletion from body losses or more commonly as a sequel to the redistribution of phosphate from the extracellular to the intracellular compartment. Hypophosphatemia is a multisystem disturbance capable of involving the neurological, immunological, and muscular systems, among others. In this report, we describe five patients with severe head injury who developed marked hypophosphatemia (less than 1 mg/dl) within 24 hours of hospitalization. This fall in serum phosphate coincided with the induction of respiratory alkalosis consequent to mechanical ventilation. In four of the five patients, as acid-base parameters returned to normal, serum phosphate values rose, in all instances reaching values greater than 2.5 mg/dl. Urinary phosphorus excretion, ordinarily negligible after hypophosphatemia induced by hypocapnia, was still present in Cases 1 and 4 (greater than 600 mg/24 hours). This is unexplained by any of the known hormonal or fluid alterations that accompany head injury. These five patients developed severe, yet transient, hypophosphatemia that resolved upon correction of hyperventilation-induced acid-base abnormalities. We discuss the pathophysiology of this entity and the implications for the head trauma patient.