As reported, the incidence of chronic kidney disease (CKD) in China is 8.2% (1).Renal biopsy has been considered the gold standard for the diagnosis of pathologic kidney diseases since the early 1950s (2). This minimally invasive procedure involves extracting a small sample of kidney tissue for microscopic examination. It allows for the precise identification of pathological changes in the glomeruli, which are crucial for determining the type and severity of the disease. The biopsy provides valuable information that guides the selection of appropriate treatment strategies, thereby improving patient outcomes. Despite the potential risks associated with the procedure, its benefits in accurately diagnosing and managing chronic kidney diseases are undeniable.

However, hemorrhage is the main complication of kidney biopsy. Post-biopsy hemorrhage can range from minor hematuria to severe bleeding requiring intervention. Immediate management typically involves monitoring the patient’s vital signs and ensuring they are hemodynamically stable. In some cases, blood transfusions or even surgical intervention may be necessary. As Quan Yao Ho reported, the incidence of gross hematuria is 3.18%, 0.31% require blood transfusion treatment after kidney biopsy, and 1.63% have perirenal hematoma (3). There are significant individual differences in kidney biopsy bleeding. The high-risk group has a bleeding risk 75 times higher than the low-risk group, especially for patients with renal insufficiency (4). The risk of complications after renal biopsy in hospitalized patients is higher than previously reported, and several factors such as low platelet count, female gender, and high BUN are associated with this risk (5). Therefore, efforts are being made to reduce the incidence of kidney biopsy bleeding.

Desmopressin, also known as deamino-8-D-arginine vasopressin (DDAVP), is a synthetic analog of the hormone vasopressin. It is used to treat conditions like diabetes insipidus and hemophilia by reducing urine output and promoting blood clotting, respectively. Administered as a nasal spray or injection, desmopressin helps manage fluid balance and supports the body’s natural healing processes. desmopressin is utilized in the context of renal biopsy to mitigate bleeding risks, particularly in patients with compromised platelet function or those with uremia. It functions by elevating levels of von Willebrand factor and factor VIII, which aid in clotting and reduce bleeding time (6, 7). Some doctors routinely use hemostatic drugs such as desmopressin to prevent major bleeding before kidney biopsy, but whether they are effective is debatable. There is insufficient evidence to support the benefit or harm of desmopressin use pre-renal biopsy to reduce the risk of post-renal biopsy bleeding (8).

Earlier systematic reviews (9)(e.g., Lim et al., 2021) were inconclusive due to critical limitations: (1) inclusion of only 2 RCTs (n=197) with underpowered analyses; (2) failure to stratify by administration routes, despite known pharmacokinetic differences between intranasal/IV formulations; (3) exclusion of observational studies, thereby ignoring real-world safety signals like hyponatremia.

In recent years, there have been related research reports, therefore, this Meta-analysis focuses on the existing studies to see whether using desmopressin before kidney puncture can reduce bleeding or not, and to study the safety of hemostatic drugs.

This systematic review and meta-analysis was registered on PROSPERO (CRD4202339 1915) and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (10).

Kidney biopsy is considered to be the gold standard for diagnosing chronic kidney disease (CKD) and is crucial for developing treatment strategies (25). However, this invasive procedure carries the risk of bleeding complications (3). The use of desmopressin prior to the biopsy has been proposed to mitigate this risk, yet the evidence remains inconclusive. In this meta-analysis, we aim to synthesize the existing research findings to evaluate the efficacy of desmopressin in reducing bleeding complications associated with kidney biopsies. By analyzing data from multiple studies, we will assess the overall impact of desmopressin on bleeding risk and its implications for clinical practice. Our results may provide valuable insights for nephrologists regarding the pre-biopsy management of patients, potentially boosting the safety of this essential diagnostic procedure.

However, after analyzing 12 studies, we found something. While there appears to be a trend toward reduced bleeding rates with the use of desmopressin, this difference did not reach statistical significance. Therefore, we cannot conclude that desmopressin effectively decreases bleeding complications associated with kidney biopsies. The lack of a conclusive finding may be attributed to the considerable heterogeneity among the included studies (I ² = 79%), which could influence the reliability of our results. The substantial heterogeneity likely stemmed from: 1. Clinical diversity: Varied definitions of bleeding events (e.g., minor hematuria vs. transfusion-requiring hemorrhage), needle gauges (16G vs. 18G), and patient risk profiles. 2. Methodological biases: 10 of 12 included studies were observational, risking confounding by indication (e.g., desmopressin preferentially given to high-bleeding-risk patients). 3. Route-dependent pharmacokinetics: Differing bioavailabilities of intranasal (10 – 20%) vs. IV (100%) formulations may partly explain subgroup contrasts, but dose-response relationships could not be examined. Therefore, we conducted a very detailed subgroup analysis.

We assessed robustness through sensitivity analysis excluding individual studies. In our analysis of the 12 studies, we identified the study by Ambarish Athavale in 2019 exhibited substantial bias, with a relatively high moderate risk of bias score. After excluding one outlier study (Athavale et al., 2019), a post-hoc analysis suggested a potential signal toward reduced bleeding (pooled OR 0.63, 95%CI: 0.44 – 0.89), though this remains secondary to the primary null finding and requires validation in dedicated trials. Additionally, the heterogeneity among the remaining studies decreased significantly, indicating a more consistent effect across these analyses (pooledOR 0.63; 95%CI: 0.44 to 0.89; I ² = 64%; p=0.009). The null findings regarding desmopressin’s efficacy should be interpreted with caution. Our in-depth analysis identified critical methodological concerns: First, confounding by indication likely occurred through preferential DDAVP administration to high-bleeding-risk patients, potentially obscuring therapeutic benefits. Second, unaddressed population heterogeneity was evident—while renal-impaired patients (serum creatinine ≥1.8 mg/dL) might benefit, low-risk cohorts exhibited paradoxically increased bleeding. Third, the composite endpoint’s susceptibility to hemodilution effects (particularly hemoglobin drop ≥1 g/dL) may have inflated bleeding rates artifactually. These limitations collectively explain the counterintuitive conclusion.

This finding supports the potential benefit of desmopressin in minimizing bleeding risks during kidney biopsies and suggests that it may be a valuable consideration in the pre-procedural management of patients.

It is well-known that renal insufficiency is a significant risk factor for bleeding complications during kidney biopsy procedures. Professor Ragnar Palsson, in his study (26), also noted that kidney biopsy is generally well-tolerated by most individuals. However, he identified that an estimated glomerular filtration rate (eGFR) of less than 30 mL/min is a risk factor for postoperative hemoglobin decline. This highlights the importance of assessing renal function prior to the procedure, as patients with severely compromised kidney function may be at an increased risk for complications. Therefore, we divided participants in the study into subgroups of individuals with renal insufficiency and the general population for subgroup analysis. However, no statistical differences were found. This is inconsistent with our expectations. It may be because patients with renal insufficiency have limited response to drugs, and the protective effect of the drug is less than the risk of bleeding caused by renal insufficiency, so the outcome was not altered.

As concluded in Tingting Zhan’s study (27), the use of a 16G puncture needle is associated with a higher overall incidence of complications compared to an 18G needle. Consequently, we classified the studies based on the type of puncture needle used. Because I² is more than 50, using the Random model, it can be seen that the use of desmopressin before kidney biopsy seems to be beneficial in preventing postoperative bleeding, but the statistical difference has not been reached ( Supplementary Figure 9 ). Further expansion of the sample size is needed to determine whether desmopressin has a protective effect before kidney biopsy.

The use of desmopressin in the field of nephrology has a long history. Common administration methods include intravenous injection, nasal spray, and oral administration. Due to the differences in administration routes and dosages, and to reduce heterogeneity among studies, we categorized the studies into two groups: intravenous administration (0.3 µg/kg) and nasal spray. As a result, we found the effect of desmopressin was more pronounced in the nasal spray medication group ( Figure 4 ). Nasal sprays are more effective because they avoid the first-pass effect.

Because of the more rigorous design of randomized controlled trials (RCTs), the results are more reliable. We found that the conclusions in RCT studies were consistent, indicating that desmopressin can reduce bleeding complications associated with kidney biopsies. Similar conclusions were also observed in the low-bias group ( Figures 5 , 6 ).

desmopressin is an antidiuretic drug that augments the kidney’s reabsorption of water, particularly in the collecting ducts. The following are some of the main reasons for low sodium levels (hyponatremia) associated with desmopressin. desmopressin increases the reabsorption of water in the renal tubules, leading to water retention in the body. This can give rise to plasma dilution, which in turn causes hyponatremia. When desmopressin is used, if the patient consumes excessive amounts of water, the occurrence of hyponatremia may be exacerbated. As the kidneys cannot effectively excrete the excess water, the sodium concentration in the blood decreases. The risk factors for hyponatremia include advanced age, presence of comorbidities, use of concurrent medications, and a reduction in estimated glomerular filtration rate (eGFR) (28).

The primary strength of our review lies in its rigorous methodological approach, thorough search strategies, compliance with PRISMA guidelines, and detailed assessment of the risk of bias. Nonetheless, several limitations should be recognized. We identified a potential risk of publication bias, as indicated by the asymmetrical funnel plot and subgroup analysis. Furthermore, the high heterogeneity observed in some of our analyses, even when employing a random-effects model, suggests significant variability among the included studies that cannot be attributed solely to random chance.

Therefore, we are still unable to conclude that desmopressin can effectively improve kidney biopsy bleeding. Randomized controlled trials comparing desmopressin to placebo are necessary to guide clinical decision-making. These trials should encompass patients with different levels of acute and chronic kidney impairment and should address both native and transplant biopsy contexts. Renal centers that are currently administering desmopressin prior to renal biopsies should undertake a prospective observational study to evaluate all patient outcomes following desmopressin administration. Key outcomes to assess include bleeding complications, the size of hematomas, length of hospital stay, and any complications related to desmopressin treatment.

This meta-analysis found no statistically significant reduction in overall bleeding risk with desmopressin after kidney biopsy (pooled OR 0.71, 95%CI: 0.47 – 1.09; p=0.12). Although subgroup analyses suggested potential benefits in specific contexts—such as intranasal administration (OR 0.41, 95%CI: 0.28 – 0.60) and RCT settings (OR 0.30, 95%CI: 0.17 – 0.53)—these findings require cautious interpretation due to heterogeneity and limited generalizability. Furthermore, desmopressin use was associated with a significant increase in hyponatremia risk (OR 2.14, 95%CI: 1.51 – 3.03). Given the uncertain efficacy in the broader population and clear safety concerns, routine pre-biopsy desmopressin cannot be recommended. Intranasal desmopressin should be prioritized in future trials targeting high-bleeding-risk kidney biopsy patients. Route-specific protocols should be explored in rigorously designed trials targeting high-risk subgroups.