Desmopressin Acetate Before Percutaneous Ultrasound-Guided Kidney Biopsy in Patients with Renal Failure – Is it Really Beneficial?

Introduction

Kidney biopsy is an essential tool for the diagnosis, adequate treatment, and prognosis of many primary and secondary renal diseases. The technique for percutaneous liver biopsy was adapted to the kidney by Nils Alwall and further refined by Karl and Muehrcke in 1954 who used the modified Vim–Silverman needle for kidney biopsy.[12] Currently, the use of real-time ultrasound and automated spring-loaded biopsy gun is standard practice.

The most common complication of renal biopsy is bleeding. Other complications include pain, arteriovenous fistulas, page kidney and chronic hypertension, perirenal soft tissue infection, and rarely injury of abdominal organs and urinoma if the urinary tract is punctured. The risk of bleeding is higher with lower glomerular filtration rate (GFR), vasculitis, uncontrolled hypertension, female gender, and advanced age.[34] The risk of minor bleeding episodes including self-limiting gross hematuria or small hematomas that did not need any blood transfusion or intervention ranges from 17% to 33% in a large meta-analysis of 9,474 kidney biopsies, whereas major complications, including hemorrhage requiring transfusion, angiographic intervention, nephrectomy, or death, have been reported in only around 2% to 8% of renal biopsies.[56]

Various measures to minimize the bleeding complications of kidney biopsy such as the use of desmopressin acetate, recombinant activated factor VII, reptilase, and vitamin K1; stopping antiplatelet agents; and controlling blood pressure have been tried.[4]

The characteristic hemostatic defects in patients with renal failure are prolonged bleeding time and platelet dysfunction. Desmopressin has been shown to be effective in improving the bleeding time or in vitro tests of platelet dysfunction in at least one-half of patients and appears to act by increasing the release of large factor VIII: von Willebrand factor multimers from endothelial cells and may also increase the platelet membrane glycoprotein expression.[78] Desmopressin may be given intravenously or subcutaneously at a dose of 0.3 μg/kg (in 50 mL of saline over 15–30 minutes if intravenously), or intranasally at a dose of 3 μg/kg. DDAVP nasal spray (desmopressin acetate) is a synthetic analog of the natural pituitary hormone 8-arginine vasopressin (antidiuretic hormone [ADH]). One milliliter (0.1 mg) of intranasal DDAVP has an antidiuretic activity of about 400 IU; 10 μg of desmopressin acetate is equivalent to 40 IU. The half-life of DDAVP increases in patients with significant renal impairment.

A randomized controlled trial on the role of subcutaneous desmopressin acetate in low-risk patients undergoing kidney biopsy with creatinine <1.5 mg/dL published by Manno et al.[9] showed a significant reduction of minor complications such as hematomas. Another multicenter pilot study by Peters et al.[10] using subcutaneous desmopressin acetate (dose 0.3 μg/kg) in patients with impaired renal function (serum creatinine above 150 μmol/L) found lower major and overall complication rates in the desmopressin acetate arm.

A study on the role of low-dose intranasal DDAVP for uremic bleeding in 11 children on maintenance hemodialysis thrice a week found that the bleeding time decreased with 30 μg intranasal desmopressin dose. They hypothesized that DDAVP may be improving the platelet function at such low doses by increasing platelet serotonin uptake and ATP (adenosine triphosphate) release.[11]

Radhakrishnan et al.[12] did not find a statistically significant reduction in bleeding for patients receiving preprocedural DDAVP in patients with GFR <60 mL/minute/1.73 m² in their study. However, in patients with an estimated glomerular filtration rate (eGFR) <15 mL/minute/1.73 m², there was a trend toward a benefit for the role of DDAVP, but the numbers were small.

The aim of this study was to compare the rate of all bleeding complications (major and minor) in patients who received prebiopsy intranasal desmopressin as compared to those who did not.

Materials and Methods

This was a retrospective, single-center, study conducted at Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, India, between July 2014 and June 2018. Patients who underwent percutaneous renal biopsies in this period at our center formed the subject of study. Of these, consecutive patients with renal failure and eGFR < 30 mL/minute/1.73 m² were included in the study. Patients' demographic data, indications for biopsy, laboratory reports, and clinical and hemodynamic parameters were collected from the electronic medical records and their individual files. All patients included had normal coagulation parameters (bleeding time was not measured) and platelet count >100 × 10³/μL. Anticoagulation and antiplatelet drugs were routinely withdrawn before kidney biopsy at our center 7 days before the biopsy.

Exclusion criteria included deranged coagulation parameters or thrombocytopenia, small-sized kidneys, multiple bilateral cysts, horseshoe kidney, hydronephrosis, pyelonephritis, perirenal abscess, uncontrolled blood pressure, and patients who did not give consent. Patients whose intranasal route was compromised due to nasal congestion, discharge, severe atrophic rhinitis, impaired consciousness, and patients whose serum sodium level was <130 mmol/L were not given desmopressin.

Patients who underwent kidney biopsy from 2014 to 2016 when desmopressin was not routinely used at our center and patients who could not be given desmopressin due to local complications or hyponatremia were included in the “no desmopressin” group.

Intranasal desmopressin was used before 307 biopsies, whereas 125 patients did not receive desmopressin. The dose of intranasal desmopressin used was 40 μg puffs in each nostril, given twice – the first dose an hour before and the second one 15 minutes before the biopsy (cumulative dose of desmopressin = 160 μg).

The kidney biopsies were performed using a percutaneous technique with real-time ultrasonography imaging and needle tracking guide (Ultra-pro II™ Needle guide, Civco, Iowa, USA) on a Toshiba, Japan, Xario model SSA-660a, with a 3.75-MHz curvilinear probe. All biopsies were performed by a nephrologist and a trainee nephrologist. The American Society of Diagnostic and Interventional Nephrology requires nephrologists to have completed each procedure as a primary performer a minimum of 25 times to be certified, and the nephrology trainees at our institute are adequately trained and have performed kidney biopsies that exceed this number many times over. The biopsies were taken using automated spring-loaded devices (Bard Peripheral Vascular Inc., USA, BARD^® Max-core™ disposable core biopsy needle) with 18 gauge, and 16-cm long needle with a penetration depth of 22 mm and a sample notch of 18 mm.

All patients were advised to lay supine in the bed with a compression bandage over the biopsy site for at least 6 hours with overnight bed rest and close monitoring of urine for gross hematuria, blood pressure, and pulse rate. Hemoglobin and hematocrit were measured after 6 hours and 24 hours of the biopsy. A screening ultrasound was done immediately after the biopsy by the nephrologist performing the procedure. Repeat ultrasound or computed tomography was done by a radiologist if any signs or symptoms of a bleeding complication such as a significant decrease in hemoglobin, hypotension, flank pain, or hematuria were present.

Patient-related information was collected from the hospital informatics system. This study was approved by the Institutional Ethics Committee, and prior informed consents were obtained from all patients.

Results

Discussion

In our single-center, retrospective study of patients with eGFR <30 mL/minute/1.73m² who underwent percutaneous kidney biopsy under ultrasound guidance, prebiopsy intranasal administration of desmopressin was associated with a significantly lower overall rate of bleeding complications (12.37% vs. 20.80%; P = 0.025). The decrease in minor bleeding complications in our study is consistent with the randomized controlled trial by Manno et al.,[9] where parenteral desmopressin was used in low-risk kidney biopsy patients with similar findings. This RCT did not have major bleeding complications in any patient of either group. A recent study by Athavale et al.[13] also found a lower bleeding incidence in patients with impaired renal function with intravenous desmopressin.

A study by Rao et al., which used intranasal desmopressin in patients with creatinine >1.5 mg/dL (excluding patients on dialysis), found a reduced risk of minor but not major complications consistent with our study.[14] This study had a near-universal incidence of hyponatremia in the desmopressin group, which was not seen in the current study. This may be because of the reduced antidiuretic effect of desmopressin due to the poorer renal function in our patients. However, as this was a retrospective study, information regarding mild cognitive dysfunction due to hyponatremia or a need for dialysis or ultrafiltration in case of fluid overload could not be ascertained accurately, and they were not specifically studied. As all patients in our study were inpatients, fluid intake is generally restricted in patients with significant renal failure, and a previous study shows that a single dose of desmopressin may not lead to hyponatremia unless concomitant excessive fluid intake was present.[15]

Desmopressin use did not decrease the incidence of major post-biopsy bleeding requiring a blood transfusion or a radiological intervention including gel foam embolization or coiling in the current study. This is in line with a large retrospective cohort study by Leclerc et al.,[16] who found similar rates of symptomatic hematomas and intervention in patients given desmopressin as those who did not receive desmopressin. A recent systematic review also found insufficient high-quality evidence to support the routine use of desmopressin before the biopsy.[17]

Therefore, the benefit of desmopressin in decreasing bleeding complications after renal biopsy seems restricted to minor hematomas or gross hematuria that resolve spontaneously and do not seem to extend to major complications that require transfusion or intervention. This may be due to the many variables that increase a patient's risk of bleeding, including age, gender, obesity, blood pressure, histological diagnosis, coagulation abnormalities, and poor technique that remain unaffected by desmopressin. When a patient had bleeding stemming from a pseudoaneurysm or an arteriovenous fistula, a correction of uremic hemostatic disorders by desmopressin may not be enough to contain the bleeding. These are possible reasons to explain the lack of benefit with desmopressin to prevent major bleeding complications.

The drawbacks of our study include its retrospective nature, single-center design, small numbers, and inclusion of only patients with eGFR <30 mL/minute/1.73 m². The response to desmopressin was not measured in our study using bleeding time and platelet function analyzer, and a cost–benefit analysis was also not done.

Unlike many studies, our study has used intranasal desmopressin before renal biopsies, and whether the lack of benefit with desmopressin in reducing major complications is due to lower bioavailability needs to be studied. Therefore, further extensive, prospective studies are needed to clarify the optimal desmopressin route and dose and its complications including severe hyponatremia and thrombosis. Also, desmopressin nasal spray retails for more than INR 600 ($8) in India, and a cost–benefit analysis is needed before prescribing its routine use.

Conclusion

Intranasal desmopressin use in patients with eGFR <30 mL/minute/1.73 m² who underwent percutaneous renal biopsy was associated with a decrease in the overall rate of bleeding complications but did not decrease the rate of major bleeding episodes and need for intervention. The ideal dose and route of desmopressin and its role in patients across various stages of renal dysfunction are areas for future research.