This week, as an emergency chat, we will discuss some hot-off-the-press data. Published a few days ago, the first look at what happens in the kidneys.

Apr 14, 2020

Introduction

Percutaneous kidney biopsy remains an essential diagnostic procedure in nephrology. Despite advances in ultrasound guidance and the use of diverse biopsy devices, post-biopsy bleeding remains a critical concern. Bleeding complications range from minor events (hematuria or hematomas) to major events requiring interventions. Risk factors for native kidney biopsy procedure-induced bleeding include reduced eGFR, hypertension, anemia, female sex, and uremic platelet dysfunction (Schnuelle P, J Clin Med 2023; Athavale A et al, BMC Nephrol 2019; Manno C et al, AJKD, 2011). Interestingly, the type of glomerular lesion seen subsequently on biopsy does not alter the risk of bleeding complications.

When discussing the risk of bleeding with patients undergoing native kidney biopsies it has been estimated that roughly 1 in 100 patients may require a blood transfusion, 1 in 1000 may require an intervention like transcatheter embolization, and 1 in 10,000 may require a nephrectomy to control bleeding (rule of 10s). The table below, from a multi-year nationwide Japanese study, gives estimates for bleeding complications and/or treatments. Fortunately, no nephrectomies were required in >15,000 biopsies over a three-year period, confirming the rarity of the most severe potential complications (Kawaguchi T et al, Clinical and Experimental Nephrology 2020).

Table 7. Bleeding complications of percutaneous native kidney biopsy in Japan. Clinical and Experimental Nephrology. Kawaguchi T et al, 2020.

Desmopressin (1-deamino-8-D-arginine vasopressin, or DDAVP) is a synthetic analog of vasopressin with potent hemostatic properties, widely used in the management of bleeding disorders associated with CKD. Unlike vasopressin, desmopressin is selective for V2 receptors on endothelial cells, where it activates a cAMP-mediated pathway leading to the exocytosis of von Willebrand factor (vWF) and Factor VIII. This enhances platelet adhesion and aggregation, improving primary hemostasis, particularly in patients with uremia-associated platelet dysfunction. Its effects begin within 30 to 90 minutes of administration and typically last 4 to 8 hours, making it a theoretically ideal pre-procedural agent for high risk individuals undergoing kidney biopsy (Kaufmann JE et al, J Clin Invest 2000, Kaufmann JE et al, J Thromb Haemost 2003, Ozgönenel B et al Postgrad Med J 2007).

Adapted from: DDAVP in the treatment of platelet dysfunction. Yartsev, A. Deranged physiology, 2015.

While desmopressin has long been considered a logical intervention for patients undergoing kidney biopsy, clinical data is much more uncertain. Previous studies have suggested that while desmopressin may reduce minor bleeding events, such as transient hematuria or small hematomas, its effect on preventing major complications remains unclear and inconsistent. Some randomized trials and observational studies have reported benefit in selected high-risk populations, while others have shown no effect or even paradoxical harm, particularly in patients not clearly defined as high-risk (Sattari et al, Iran J Kidney Dis 2022; Manno et al, Am J Kidney Dis 2011; Sethi J, Indian J Nephrol 2024; Jose L et al, Indian J Nephrol 2022).

These discrepancies have raised important questions around the patient selection, optimal dosing, and timing of desmopressin administration. Against this background of uncertainty, Prasad et al, KI Reports 2025 and Chakrabarti et al, Kidney360 2025, reexamine the role of desmopressin in post kidney biopsy bleeding in their respective RCTs. Beyond examining clinical outcomes, these contemporary trials challenge current assumptions regarding both the efficacy and safety of incorporating desmopressin into routine biopsy procedures.

The Studies

Methods

Study design and population
Both single center trials, conducted in two different cities in India, employed a randomized, double blind, placebo-controlled trial design. Prasad et al included patients across all eGFR ranges (with pre-stratification at the 30 mL/min cutoff). Chakrabarti et al exclusively enrolled higher-risk patients with eGFR ≤60 mL/min. Both studies excluded patients with hyponatremia, and transplant graft biopsies. More details of the eligibility can be seen in the infographic below.

Procedural standardization
While both studies employed ultrasound-guided biopsy techniques, Prasad et al maintained stricter standardization with a fixed 18G needle size and passes to get two cores of tissue, whereas investigators from Chakrabartiet al trial were more permissive with the number of passes and use of the 16G kidney biopsy needle. Note that the trial conducted by Prasad et al was triple-blinded (patients, operators, outcome assessors), while the Chakrabarti study was blinded for patients and operators.

Dosing and monitoring
The two studies chose different approaches regarding desmopressin dose (fixed 300 mcg intranasal dose in Prasad et al, 3 mcg/kg in Chakrabarti et al). Moreover, Prasad et al monitored factor VIII and von Willebrand factor levels, for a more mechanistic understanding.

Outcomes
The primary outcome in both trials was the occurrence of post biopsy bleeding, including major and minor bleeding. Major bleeding was defined as need for transfusion, any intervention, or death and minor bleeding as gross hematuria or perinephric hematoma.

Power size and sample calculation

Prasad et al used a conservative 16.8% absolute risk reduction based on prior evidence (Manno C et al, AJKD, 2011), while Chakrabarti et al assumed a more optimistic 32% risk reduction (Sattari SA, et al, AJKD, 2022).
In Prasad et al study, the sample of 203 patients provided 80% power to detect their pre-specified effect size of 16.8%. Chakrabati et al demanded 95% power of a larger, 30% effect size, requiring fewer patients (152), but leaving the study vulnerable when the actual effect was smaller.

Funding sources: Both studies were funded by internal institutional funding.

Results

Both trials enrolled the required number of participants - with some notable differences. The Prasad et al trial (right) required to screen over 1200 patients over 4 years to enrol ~ 200 patients, while Chakrabarti et al (left) managed to enrol their ~ 150 participants from only 272 (with no one refusing to consent).

Baseline characteristics of the desmopressin groups in the trials by Prasad et al and Chakrabart et al, are shown in the following combined table. Both trials enrolled relatively young cohorts with comparable BMIs. Notable differences existed in kidney function and hematologic parameters. Dialysis exposure prior to biopsy was shown in the Chakrabarti et al study (57%), while this data is not available for the study by Prasad et al (65 patients with eGFR < 15, but dialysis was not specifically noted).

Adapted baseline characteristics Table 1 from Prasad et al and Chakrabarti et al

Outcomes

Both trials assessed the effect of desmopressin on post-kidney biopsy bleeding complications. In Prasad et al, desmopressin significantly reduced overall bleeding incidence (11.9% vs. 33.3%) with a RR 0.36 (95% CI: 0.20-0.65; p = 0.0007), showing the greatest benefit in patients with reduced eGFR. In contrast, Chakrabarti et al, which enrolled only patients with eGFR ≤60 mL/min/1.73m², showed no statistically significant difference in bleeding between the desmopressin and placebo groups (36% vs. 47%) with a RR 0.77 (95% CI: 0.52–1.13; p = 0.17). Thus both trials reported a higher risk of bleeding in the control group compared to their assumptions (33% observed versus 16.8% assumed in Prasad et al, and 44% observed versus 33% assumed in Chakrabarti et al). Most of the outcome events were comprised of perinephric hematomas with very few major bleeding incidents (see below).

Secondary Outcomes
In Prasad et al, secondary outcomes such as reduced hematoma formation, elevated vWF and Factor VIII levels, and lower incidence of hypotension favored desmopressin. However, treatment was associated with a higher frequency of hemoglobin drop, hyponatremia, and headache. In contrast, Chakrabarti et al focused on perinephric hematoma size at 6 and 24 hours, showing more frequent resolution at 24 hours in the desmopressin group. Nonetheless, minor and major post-biopsy complications beyond bleeding did not differ significantly between groups.

Subgroups
In Prasad et al, among patients with eGFR >30 ml/min/1.73m², bleeding incidence was significantly lower in the desmopressin group (5.9%) compared to placebo (23.5%) (RR 0.25; 95% CI: 0.075–0.83; p = 0.02). A similar benefit was observed in those with eGFR <30 ml/min/1.73m², where desmopressin reduced bleeding to 18% versus 43.1% in the placebo arm (p = 0.006). These subgroup findings suggest a potential protective effect of desmopressin across varying degrees of kidney dysfunction, though no p value for interaction is presented and there is overlap between the 95% CI. The authors reported a number needed to treat (NNT) of 5.7 to prevent one bleeding event, but whether this estimate holds more broadly or only in carefully selected patients, remains open to debate. In contrast, Chakrabarti et al included only patients with eGFR ≤60 ml/min/1.73m² and did not stratify bleeding outcomes by renal function, limiting deeper subgroup insights.

Adapted from Table 3: Post-biopsy bleeding stratified by eGFR category. Prasad et al, KI Reports 2025.

Safety and Mechanistic Insights

In terms of safety, desmopressin was generally well tolerated, with no serious adverse events or deaths reported. Nasal discomfort, hyponatremia, and headache occurred more frequently in the desmopressin group (28.7% vs. 5.8%, and 7.9% vs. 1.9%, respectively) in the Prasad et al study. There was also a higher incidence of asymptomatic hyponatremia in the Chakrabarti et al study (serum sodium 130 versus 133). Pharmacologically, desmopressin produced a significant but transient rise in Factor VIII and vWF levels at 2 hours, supporting its proposed mechanism in enhancing platelet adhesion. However, these elevations declined by 4 hours. These findings set the stage for a broader discussion on desmopressin’s role, and limitations, in kidney biopsy bleeding prevention.

Adapted from Table 6 and figure 6: Effect of desmopressin on factor VIII and vWF levels. Prasad et al, KI Reports 2025.

Discussion

Should desmopressin be routinely used to prevent post-biopsy bleeding in patients with reduced kidney function? This question remains central to nephrology practice, as both observational studies and randomized trials show mixed results. The recent RCTs by Prasad et al and Chakrabarti et al revisit this debate, providing new insights into the efficacy and safety of desmopressin across different degrees of chronic kidney disease.

The lower overall rates of bleeding observed by Prasad et al (22.6%) compared to Chakrabarti et al (42.1%) may be related to fundamental differences in methodology- 18G vs 16G needles, fewer needle passes in the former, use of an ultrasound needle guidance, and having two operators performing the biopsy versus a single operator in the latter study. While prior evidence suggests no significant difference in the number of sampled glomeruli, larger hematomas and higher arteriovenous fistulas have been reported with the use of 16G needles (Ramos Botelho et Al, Int J Uro 2018, Xu S et al, Int Urol Nephrol 2022). This raises the possibility that Chakrabarti et al's higher hematoma burden may reflect higher risk procedural factors rather than intervention failure. Interpretation of risk mitigation was further complicated by inclusion of patients with eGFRs <60ml/min/1.73m2, use of a lower desmopressin dose (purportedly below the threshold to reliably release vWF), and ~50% patients having received dialysis prior to biopsy which may have indirectly affected bleeding risk (Sreedhara et al, AJKD 1995).

While smaller hematoma sizes and faster resolution have been noted in studies with desmopressin use (Sattari et al, Iran J Kidney Dis 2022; Manno C et al, AJKD 2011), the clinical impact of differences in hematoma size or hematoma resolution at 24 or 48 hours remains unclear. Have these surrogate markers translated into improved safety, fewer interventions, or shorter hospital length of stay? One may intuitively find oneself favouring desmopressin in view of these softer end-points. The reality is we may end up prolonging hospitalizations, ordering more serial imaging and hemograms, and fervently watching the patient in ‘non-major’ bleeding events.

On the other hand, a therapy that appears safe, without any serious adverse events or symptomatic hyponatremia, may seem justified for use in high-risk groups. After all, despite the lack of significance - the direction in both trials was towards a lower incidence of (mostly minor) bleeding. Though neither of the two trials defines the ideal patient where stands to benefit the most from desmopressin, there appears to be a somewhat dubious signal advocating its use in patients with lower eGFRs. Clearly, universal pre-biopsy desmopressin use is not warranted. An individualized approach, guided by the bleeding risk, kidney function, and patient characteristics, may be the more pragmatic risk/benefit approach. More robust evidence is needed to define optimal timing, dosing, and patient selection, which can only be made possible by thorough investigations of the miscreant pathology of hemostasis.

As a final note, many nephrologists do not perform kidney biopsies once they have completed fellowship training. Interventional radiologists now perform a large number of these procedures, although there is a great amount of variability geographically. If we are convinced that certain high-risk patients would benefit from desmopressin, it will be increasingly important for nephrologists to advocate for patients to proceduralists about the use and timing of desmopressin in specific cases.

Conclusion

Desmopressin’s pharmacological hemostasis is mechanistically supported by the current studies. Desmopressin does decrease minor inconsequential bleeding, with minor (mostly) inconsequential adverse events. It appears from the current evidence that treatment with ddAVP makes you feel you have done ‘something’, without (unfortunately) reducing the risk of clinically important major bleeding events.

Double Trouble: ddAVP and the Bleeding Biopsy

#NephJC Chat

Tuesday, May 13, 2025, 9 pm Eastern on Bluesky

KI Reports, published online April 17, 2025, DOI: 10.1016/j.ekir.2025.04.019

Randomized Double-Blind Placebo-Controlled Trial of Desmopressin for Post–Kidney Biopsy Bleeding

Effect of Desmopressin on Post Kidney Biopsy Bleeding Complications in Patients with Reduced Kidney Function: A Randomized Controlled Trial

Introduction

The Studies

Methods

Results

Discussion

Summary prepared by

Cristina Popa, Milagros Flores, Sayali Thakare

Reviewed by

Brian Rifkin, Swapnil Hiremath