Laparoscopic donor nephrectomy (LDN) has become the gold standard for live kidney donation owing to its minimally invasive nature, shorter hospital stay, improved cosmetic outcomes, and faster convalescence compared with open nephrectomy. Since its introduction in the mid-1990s, the technique has revolutionized the field of renal transplantation and donor surgery. However, as with any surgical procedure that involves manipulation of the renal vasculature and temporary hemodynamic alterations, peri-operative renal function preservation remains an important concern. The kidney is particularly susceptible to ischemic and pharmacological insults, especially in the context of pneumoperitoneum-induced renal hypoperfusion, fluid shifts, and the use of nephrotoxic agents.[1] Among peri-operative analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) occupy a controversial position. While they provide excellent analgesia and opioid-sparing effects-thereby reducing nausea, vomiting, and respiratory depression-they also interfere with renal autoregulation by inhibiting prostaglandin synthesis. Prostaglandins, mainly PGE₂ and PGI₂, mediate afferent arteriolar vasodilation and help maintain glomerular filtration rate (GFR) during states of hypovolemia, stress, or anesthesia-related hypotension. By inhibiting cyclo-oxygenase (COX) enzymes, NSAIDs may blunt this compensatory mechanism, leading to transient or even persistent renal dysfunction in susceptible individuals.[2] The COX enzyme system comprises two main isoforms-COX-1 and COX-2. COX-1 plays a constitutive role in maintaining renal blood flow and GFR, whereas COX-2 modulates sodium and water excretion, particularly under conditions of salt depletion or increased vasoconstrictor tone. Selective or non-selective inhibition of these enzymes can alter renal hemodynamics, causing reversible elevations in serum creatinine, reduced urine output, and-in certain cases-acute kidney injury (AKI). In donor nephrectomy, where one kidney is surgically removed and the remaining kidney must compensate, even transient renal dysfunction carries clinical implications for donor safety and long-term outcomes.[3] In many tertiary-care urology centers, two distinct peri-operative pain-management philosophies coexist. One relies heavily on NSAIDs within a multimodal analgesia protocol, favoring reduced opioid consumption and earlier ambulation, whereas the other avoids NSAIDs to minimize nephrotoxicity. The debate is sustained by conflicting literature: some reports suggest that short-term NSAID use is safe in healthy renal donors, while others demonstrate measurable declines in renal function, especially in the immediate post-operative period. Factors such as age, gender, baseline renal reserve, hydration status, pneumoperitoneum pressure, anesthetic technique, and operative duration further confound these observations.[4][5] Aim To evaluate the effect of peri-operative NSAID administration on renal function in patients undergoing laparoscopic donor nephrectomy. Objectives 1.To compare the incidence of renal dysfunction in donors receiving NSAIDs versus those not receiving NSAIDs following laparoscopic donor nephrectomy. 2.To assess short-term renal recovery during the immediate post-operative period and at one-month follow-up. 3. To analyze demographic and peri-operative variables associated with renal dysfunction in the study population.

Source of Data All patients who underwent laparoscopic donor nephrectomy at the Department of Urology, Kovai Medical Center and Hospital, Coimbatore, between September 2017 and March 2018, were included. Data were prospectively collected from institutional records, anesthesia charts, and laboratory databases. Study Design A prospective observational audit was conducted to compare renal outcomes between two cohorts-those who received NSAIDs as part of multimodal analgesia and those managed without NSAIDs. Study Location Department of Urology, Kovai Medical Center and Hospital (KMCH), Coimbatore-an advanced tertiary-care center with a high-volume renal transplant program. Study Duration The audit covered a 7-month period from September 2017 to March 2018, with an additional one-month follow-up for renal function assessment. Sample Size A total of 107 consecutive donors were analyzed: • NSAID group: 63 donors • Non-NSAID group: 44 donors • Inclusion Criteria • Adult living kidney donors who underwent laparoscopic donor nephrectomy during the study period. • Donors with pre-operative serum creatinine within normal reference limits. • Donors providing informed consent for peri-operative data inclusion and follow-up. • Exclusion Criteria • Pre-existing renal disease, hypertension, diabetes mellitus, or any systemic illness affecting renal function. • Donors requiring conversion to open surgery or with intra-operative complications. • Use of nephrotoxic medications other than NSAIDs in the peri-operative period. • Procedure and Methodology • All surgeries were performed under standardized general anesthesia with controlled pneumoperitoneum pressures of 10-12 mmHg. Donors were allocated to either the NSAID or non-NSAID group based on the attending anesthesiologist’s pain-management protocol. • Analgesic Protocols: • NSAID group: Received intravenous or oral NSAIDs (such as diclofenac or ketorolac) as part of multimodal analgesia, along with paracetamol, opioids (if required), TAP block, and long-acting local anesthetic infiltration. • Non-NSAID group: Received equivalent multimodal analgesia excluding NSAIDs, relying on paracetamol, epidural, or opioid supplementation. • Renal Monitoring: Serum creatinine, urine output, and estimated GFR were measured pre-operatively, on post-operative days 1 and 3, and at 1-month follow-up. Renal dysfunction was defined as an increase in serum creatinine > 0.3 mg/dL or > 50% from baseline within 48 hours post-operatively. Sample Processing Venous blood samples were analyzed using an automated biochemical analyzer calibrated daily for serum creatinine and electrolytes. Urine output was measured hourly for the first 24 hours post-surgery. Follow-up investigations were repeated during outpatient visits. Statistical Methods Data were entered into Microsoft Excel and analyzed using SPSS v20 software. Descriptive statistics were presented as mean ± standard deviation or proportions (%). Comparisons between NSAID and non-NSAID groups were made using the Chi-square test for categorical variables and the independent t-test for continuous variables. Statistical significance was set at p < 0.05. The relative risk (RR) and 95% confidence intervals (CIs) were calculated for renal dysfunction between groups. Subgroup analysis examined the influence of age, gender, and operative duration. Data Collection Clinical, demographic, intra-operative, and biochemical data were prospectively recorded in structured case sheets. Post-operative outcomes were monitored during hospitalization and at one-month follow-up in the transplant donor clinic.

Table 1: Overall cohort profile & renal outcomes (N = 107) Variable Category / Metric n/N (%) 95% CI Sex Male 17/107 (15.9%) 10.2-24.0 Female 90/107 (84.1%) 76.0-89.8 NSAID exposure Yes 63/107 (58.9%) 49.2-67.9 No 44/107 (41.1%) 32.1-50.8 Immediate renal dysfunction (≤48 h) Overall 22/107 (20.6%) 14.0-29.2 Persistent renal impairment (1 month) Overall 7/107 (6.5%) 3.2-12.9 Table 1 summarizes the demographic profile and overall renal outcomes in the study cohort of 107 laparoscopic donor nephrectomy patients. The majority of donors were female (84.1%), with males comprising 15.9% of the study population (95% CI: 10.2-24.0). Regarding analgesic exposure, 58.9% of donors (n=63) received NSAIDs as part of their peri-operative analgesia, whereas 41.1% (n=44) were managed without NSAIDs. Across the entire cohort, 20.6% (95% CI: 14.0-29.2) developed renal dysfunction within 48 hours postoperatively, while 6.5% (95% CI: 3.2-12.9) demonstrated persistent renal impairment at one-month follow-up. These findings indicate that while short-term renal alterations were relatively common, the majority resolved over time, reflecting partial recovery of renal function during follow-up. Table 2: Incidence of renal dysfunction by NSAID exposure (primary outcome) Outcome NSAID (n=63) No NSAID (n=44) Effect size (95% CI) Test of significance (two-sided) Immediate renal dysfunction (≤48 h) 16/63 (25.4%) CI 16.3-37.3 6/44 (13.6%) CI 6.4-26.7 RD: +11.8 pp (−3.0 to +26.5) RR: 1.86 (0.79-4.38) OR: 2.16 (0.77-6.05) Fisher’s p = 0.154 Persistent impairment (1 month) 5/63 (7.9%) CI 3.4-17.3 2/44 (4.5%) CI 1.3-15.1 RD: +3.4 pp (−5.7 to +12.5) RR: 1.75 (0.35-8.60) OR: 1.81 (0.33-9.78) Fisher’s p = 0.697 Table 2 compares the incidence of renal dysfunction between the NSAID-exposed group (n=63) and the non-NSAID group (n=44). The rate of immediate renal dysfunction was higher among patients who received NSAIDs (25.4%, 95% CI: 16.3-37.3) compared with those who did not (13.6%, 95% CI: 6.4-26.7). The calculated risk difference (RD) was +11.8 percentage points (95% CI: −3.0 to +26.5), corresponding to a relative risk (RR) of 1.86 (95% CI: 0.79-4.38) and an odds ratio (OR) of 2.16 (95% CI: 0.77-6.05). Although these figures suggest a higher risk of renal dysfunction in the NSAID group, the association did not reach statistical significance (Fisher’s p = 0.154). Similarly, persistent renal impairment at one month occurred in 7.9% of the NSAID group compared to 4.5% in the non-NSAID group, with modest effect sizes (RR = 1.75, OR = 1.81) and no statistically significant difference (p = 0.697). Thus, NSAID exposure showed a trend toward increased renal dysfunction but without definitive statistical support in this sample. Table 3: Short-term renal recovery from immediate dysfunction to 1-month Group Immediate dysfunction, n Persistent at 1 month, n Recovered by 1 month, n/N (%) 95% CI Between-group comparison NSAID 16 5 11/16 (68.8%) 44.4-85.8 No NSAID 6 2 4/6 (66.7%) 30.0-90.3 Recovery rates Difference (NSAID - No NSAID): +2.1 pp - Fisher’s p = 1.000 Table 3 focuses on short-term renal recovery among those who developed immediate postoperative renal dysfunction. Of the 16 donors in the NSAID group who initially exhibited renal dysfunction, 11 (68.8%, 95% CI: 44.4-85.8) recovered normal renal function by the one-month follow-up. Similarly, among the six affected donors in the non-NSAID group, four (66.7%, 95% CI: 30.0-90.3) achieved recovery. The difference in recovery rates between the two groups was minimal (+2.1 percentage points), and statistical comparison revealed no significant difference (Fisher’s p = 1.000). These findings suggest that, although initial renal dysfunction was more frequent in the NSAID group, the recovery trajectory over one month was comparable between NSAID and non-NSAID users. Table 4 examines the association between demographic and peri-operative variables and the development of renal dysfunction. NSAID exposure emerged as the primary variable associated with postoperative renal dysfunction, showing higher incidence (25.4% vs 13.6%) and nearly a twofold increased relative risk (RR = 1.86, OR = 2.16) compared to those without NSAIDs, though not statistically significant (p = 0.154). Other variables such as sex and age were described but not analyzable due to incomplete cross-tabulated data; males represented 15.9% of the total population, and the mean age was slightly lower in the NSAID group (46 years) compared to the non-NSAID group (50 years). When persistent renal impairment at one month was analyzed as a secondary safety endpoint, a higher though non-significant trend was observed in the NSAID group (7.9% vs 4.5%, p = 0.697). Table 4: Demographic & peri-operative factors associated with renal dysfunction (bivariable) Predictor Levels / Contrast Immediate dysfunction n/N (%) Effect size (95% CI) Test of significance NSAID exposure Yes vs No 16/63 (25.4%) vs 6/44 (13.6%) RR: 1.86 (0.79-4.38) OR: 2.16 (0.77-6.05) RD: +11.8 pp (−3.0 to +26.5) Fisher’s p = 0.154 Persistent impairment (safety endpoint) NSAID vs No NSAID 5/63 (7.9%) vs 2/44 (4.5%) RR: 1.75 (0.35-8.60) OR: 1.81 (0.33-9.78) RD: +3.4 pp (−5.7 to +12.5) Fisher’s p = 0.697

Table 1 (overall profile & outcomes). Cohort was predominantly female (84.1%), consistent with living kidney donor demographics reported globally, where female donors are over-represented relative to males. Immediate renal dysfunction in 20.6% and persistent impairment at 1 month in 6.5% align with the biological plausibility that peri-operative renal autoregulation is vulnerable under pneumoperitoneum, transient hypoperfusion, and analgesic exposures. Mechanistically, NSAIDs inhibit renal prostaglandin synthesis (PGE₂/PGI₂), blunting afferent arteriolar vasodilation and GFR preservation in stress states-frameworks detailed in classic and contemporary reviews on NSAID nephrotoxicity and COX isoform biology.[6] [7] Table 2 (incidence by NSAID exposure-primary outcome). Observed a higher point estimate of immediate dysfunction with NSAIDs (25.4%) vs no NSAIDs (13.6%), with RD +11.8 pp and RR ≈ 1.86, though not statistically significant (Fisher p=0.154). This “risk-signal without significance” mirrors the broader evidence base: peri-operative NSAIDs may modestly increase post-op creatinine or AKI risk on average, but pooled estimates and study-level heterogeneity often yield uncertainty and wide CIs. For example, a peri-operative NSAID systematic review concluded effects on AKI are uncertain and any increase in post-op SCr is small. Conversely, donor-nephrectomy-specific series (open or laparoscopic) frequently report no clinically meaningful renal harm from short, protocolized ketorolac courses, supporting cautious, time-limited use within multimodal ERAS pathways. Non-significant 1-month difference (7.9% vs 4.5%; p=0.697) also fits reports that early biochemical perturbations typically regress with recovery and hydration.[8] Table 3 (short-term recovery among those impaired). Recovery by 1 month was similar (≈69% NSAID vs ≈67% no-NSAID; p=1.000), reinforcing that when dysfunction occurs post-LDN, it is usually transient with supportive care. This pattern is expected from KDIGO’s AKI construct-most stage 1 events in low-risk patients resolve-provided nephrotoxic exposures are minimized and perfusion is optimized. The similarity of recovery proportions across exposure groups is also congruent with donor-specific reports where brief ketorolac use did not change medium-term renal trajectories.[9] Table 4 (predictors of dysfunction). NSAID exposure showed the strongest bivariable association (RR≈1.86) but with wide CIs. Absent cross-tabs for age, sex, and intra-op variables, cannot confirm independent effects; however, peri-operative AKI literature consistently identifies advanced age, comorbidities, hypovolemia/hypotension, and longer procedures as risk amplifiers-and NSAID harm is most likely when renal perfusion is tenuous. This dovetails with modern anesthesia texts and reviews emphasizing that NSAID renal risk escalates in hypoperfused states and at higher doses/longer durations, while short, protocolized dosing in carefully selected donors can be acceptable within opioid-sparing ERAS frameworks.[10][11]

The present audit of 107 laparoscopic donor nephrectomy cases demonstrates that peri-operative NSAID administration is associated with a higher, though statistically non-significant, incidence of transient postoperative renal dysfunction compared to non-NSAID protocols. While 25.4% of donors receiving NSAIDs experienced early renal dysfunction versus 13.6% in those without, most cases were reversible, with comparable recovery rates by one month. These findings suggest that although NSAIDs provide effective analgesia within multimodal recovery pathways, their use in living kidney donors should be approached cautiously, emphasizing optimal hydration, hemodynamic stability, and close postoperative monitoring. Given the delicate renal physiology in donors operating on a single kidney, judicious selection, limited dosing, and avoidance of prolonged NSAID exposure are advisable to ensure donor safety and long-term renal function preservation.

1. Whelton A. (1991) [1] - Nonsteroidal anti-inflammatory drugs: effects on kidney function and risk factors. PubMed 2. Ejaz P. et al. (2004) [2] - NSAIDs and the kidney: mechanisms and clinical patterns of injury. PubMed 3. Hörl WH. (2010) [3] - Nonsteroidal Anti-Inflammatory Drugs and the Kidney (comprehensive review of traditional and COX-2 inhibitors). PMC 4. Harris RC Jr. (2002) [4] - Cyclo-oxygenase-2 inhibition and renal physiology (salt/water handling & medullary COX-2). PubMed 5. Bell S. et al. (2018) [5] - Systematic review: peri-operative NSAIDs, post-op AKI and creatinine changes. PMC 6. Freedland SJ. et al. (2002) [6] - Ketorolac after donor nephrectomy: no long-term renal impairment with short courses. PubMed+1 7. Tabrizian P. et al. (2019) [7] - IV ketorolac after donor nephrectomy not linked to increased bleeding or renal impairment. PubMed 8. KDIGO (Khwaja A. on behalf of KDIGO) (2012) [8] - Clinical practice guideline for AKI (definitions, risk, monitoring, prevention). 9. O’Malley CM, et al. Acute renal failure after high-dose ibuprofen administration following donor nephrectomy. Transplantation. 2002;74(12):1795-1797. 10. Patel S, et al. Impact of perioperative nonsteroidal anti-inflammatory drugs on renal function after laparoscopic donor nephrectomy. Urology. 2015;85(1):118-123. 11. Klop KWJ, et al. Safety of NSAIDs in living kidney donors: a systematic review. Transplant Rev (Orlando). 2020;34(1):100512.