**2.3.2.1 Impact of clamping time**

334 Chronic Kidney Disease

Acute reduction in functional renal mass leads the remnant glomeruli to maintain the renal function by several mechanisms: adaptive glomerular hypertrophy, hyperperfusion,

NSS aims to achieve two goals: a complete excision of the tumour but at the same time guarantee an optimal preservation of renal function. With less excision of healthy renal tissue with NSS, we can expect less glomerulosclerosis and renal failure (Van Poppel et al., 2003). Therefore, NSS seems to be the best way to prevent Chronic Kidney Disease (CKD). In one of our studies on OPN for T1b renal tumours (Joniau et al., 2009), 10% of patients developed de novo renal insufficiency. Six of those seven patients had imperative indication. Serum creatinin levels dropped significantly in imperative indication, while this

In our last study of 98 open partial nephrectomies for T1b, estimated Glomerular Filtration

10.2% of patients developed CKD post-operatively, but 20.4% patients had an improved

In his study, Roos (Roos & Brenner, 2010) also observed a significant difference in eGFR at last follow up and in e GFR difference (calculated as e GFR preoperative – eGFR at last follow up). After NSS, 14.5% of patients (10) had reached an eGRF < 60ml/min/1.73m²

In a retrospective study (Lane et al., 2010) Lane studied 2402 patients with a normal preoperative kidney function (serum creatinin less or equal to 1.4 mg/dl) and compared: 1833 PN versus 569 RN. Tumour stage was pT1b or more in 31% of PN and 64% of RN. NSS even - with a warm ischemia time of longer than 31 minutes - demonstrated better renal outcomes, however patients in the RN group were older, had more co-morbidities and were

A solitary kidney is not a contra-indication for NSS. Lee (Lee 2010) reports 38 patients with solitary kidney who underwent partial nephrectomy: 53. 1% of them had a tumour larger than 4 cm and 76.3 % had post operatively a GFR more than 30 ml/min/1.73m². He noticed an acceptable complication rate: 7.9% Clavien I, 18.4% for Clavien II and 5.3% Clavien III. One patient required immediate post-operative haemodialysis and another one long term

Partial nephrectomy offers minimal reduction of renal function, but on the other hand

For small tumours, clamping the renal artery is sometimes not necessary. Resection without clamping can provide adequate oncologic surgery with a lower peri-operative complication rate and limited renal function deterioration. In the case of larger renal tumours, surgery requires in most cases an interruption of renal blood flow through pedicle clamping.

Rate (eGFR) deteriorated postoperatively on average by 1.74 ml/min/1.73m².

hypertension and hyperfiltration. These phenomena result in proteinuria.

**2.3 Renal function** 

CKD stage after surgery.

versus 44.7% (42) after RN.

**2.3.1 Renal function deterioration after NSS vs. RN** 

was not seen in elective and relative indications.

affected by larger and more aggressive tumours.

haemodialysis for a mean follow up of 20 months.

unfortunately exposes the patient to higher peri-operative risk.

**2.3.2 Surgical aspects influencing renal function preservation** 

For warm ischemia, maximal clamping time to preserve renal function was previously thought to be less than 31 minutes. Later it was suggested to try to limit warm ischemia time to less than 20 minutes (Becker et al., 2009). But Thompson goes further and states that "every minute counts". In his retrospective study, he analysed 362 patients with solitary kidneys and demonstrated that 25 minutes is the best cut-off for clamping time to make the distinction of patients at risk for acute renal failure, a GFR < 15ml /min per 1.73 m² and new-onset stage IV chronic kidney disease during follow up. Each additional minute increased this risk. The same cut off for irreversible renal damage was found in a prospective study (Funahashi 2009).

Thus we should consider 20-25 minutes to be the best cut-off to avoid adverse renal consequences, keeping in mind the shorter the clamping time the better. We should not forget that even with extended ischemia, partial nephrectomy still offers better renal function outcomes compared to RN (Lane et al., 2010).

### **2.3.2.2 Impact of clamping technique**

Regarding clamping technique, Coffin did not observed a difference in postoperative renal function between mechanical and digital clamping of the pedicle.

There is no consensus for type of clamping: arterial or "en bloc" arterial and venous clamping. It is also not known whether intermittent clamping is better than continuous.

#### **2.3.2.3 Cooling**

Kidney cooling prior to clamping can prevent cell damage. The optimal temperature to achieve this seems to be 15°C (Becker 2009).

When ischemia time is estimated to be probably more than 25 minutes, cold ischemia is a good option. The principle is to cool the kidney with ice slush for 10 minutes, after which the hilum should be clamped. Nevertheless, also cold ischemia time must be limited to the minimum. A maximum of 35 minutes has been proposed by several authors (Thompson et al 2007).

#### **2.3.2.4 Pharmacologic strategies**

In order to reduce the impact of ischemia, it is advised to provide preoperative hydration to facilitate renal perfusion and stimulate urine production. Therefore, furosemide administered intra-operatively is useful. Intravenous mannitol at a dose of 1 ml/kg has also been proven to be beneficial for optimal reperfusion (Becker et al., 2006). Weizer and his

The Role of Nephron-Sparing Surgery (NSS) for Renal Tumours >4 cm 337

Minervini (Minervini et al., 2011) retrospectively analysed 1519 patients operated for renal cell carcinoma to determine the impact of simple enucleation on oncologic outcomes: 982 underwent a standard partial nephrectomy versus simple enucleation in 537 cases. 25.9% of patients belonging to the standard partial nephrectomy group versus 21.3% of patients in the simple enucleation group had a renal cell carcinoma larger than 4 cm. PSM rate was significantly lower in the simple enucleation group (0.2%) versus the standard partial

For tumours smaller than 4 cm, pure enucleation provides long-term cancer-specific survival rates similar to RN and is not associated with a greater risk of local recurrence compared to partial nephrectomy (Carini 2006). Minervini (Minervini 2011) compared standard partial nephrectomy with simple enucleation: he could not find any significant difference between those 2 techniques after adjusting for cancer-specific survival probabilities: age at surgery (younger or older than 65 years), tumour stage (pT1a, pT1b or pT3a) and Fuhrman nuclear grades (1-2 versus 3). Patients who underwent a simple enucleation and had a Fuhrman nuclear grade 4 showed a significantly worse cancerspecific survival compared to patients who were treated with standard partial

In another publication (Carini et al., 2006), Carini and Minervini reviewed 71 simple enucleations for renal cell carcinoma with diameter 4 to 7 cm. Median follow up was 74 months. There was no peri-operative mortality and no major complications requiring reintervention. Oncologic outcomes were acceptable: 5- and 8-year cancer-specific survival rates were 85.1% and 81.6%, respectively. Tumour stage had an impact on cancer-specific survival: 5-year cancer-specific survival rate was 95.1% for tumours of 4 cm, 83.3% for stage pT1b and 58.3% for stage pT3a tumours. He reported 10 patients (14.1%) with progressive

**3.1.2.1 Positive surgical margin rate** 

nephrectomy group (3.4%) (p<0.001). **3.1.2.2 Cancer-specific survival rate** 

disease but only 4.2% with local recurrence.

nephrectomy.

**3.1.2 Simple enucleation versus standard partial nephrectomy** 

Fig. 3. Wedge Resection.

Fig. 1. Cooling.

team use the following schema: 12,5 g mannitol are administered ten minutes before resection and the same additional dose is given at removal of the clamp (Weizer et al., 2011). The use of an angiotensin-converting enzyme inhibitor such as enalapril has also been proposed. This should theoretically prevent vasospasm and induce vasodilatation. To prevent thrombosis, administration of heparin intravenously has been proposed but its benefit has not been proved.

Other important points are to maintain a normal blood pressure and hemodynamic stability in the peri-operative and postoperative period.
